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Katherine J. Franz

Chair of the Department of Chemistry
Chemistry
90346, Dept of Chemistry, 124 Science Dr., Durham, NC 27708-0346
2103 French Science Center, 124 Science Drive, Durham, NC 27708

Selected Publications


Histatin-5 interacts with cellular copper to promote antifungal activity against Candida albicans.

Journal Article Metallomics : integrated biometal science · December 2023 Histatin-5 (Hist-5) is an antimicrobial peptide found in human saliva that functions to defend the oral cavity from microbial infections, such as those caused by the fungal pathogen Candida albicans (C. albicans). Hist-5 can bind Cu in multiple oxidation s ... Full text Cite

Multiple Modes of Zinc Binding to Histatin 5 Revealed by Buffer-Independent Thermodynamics.

Journal Article Inorg Chem · May 8, 2023 Histatin 5 (Hist5) is an antimicrobial peptide found in human saliva as part of the innate immune system. Hist5 can bind several metal ions in vitro, and Zn2+ has been shown to function as an inhibitory switch to regulate the peptide's biological activity ... Full text Link to item Cite

Analysis of copper-induced protein precipitation across the E. coli proteome.

Journal Article Metallomics : integrated biometal science · January 2023 Metal cations have been exploited for their precipitation properties in a wide variety of studies, ranging from differentiating proteins from serum and blood to identifying the protein targets of drugs. Despite widespread recognition of this phenomenon, th ... Full text Cite

Intestinal mucin is a chaperone of multivalent copper.

Journal Article Cell · October 2022 Mucus protects the epithelial cells of the digestive and respiratory tracts from pathogens and other hazards. Progress in determining the molecular mechanisms of mucus barrier function has been limited by the lack of high-resolution structural information ... Full text Cite

Zinc Binding Inhibits Cellular Uptake and Antifungal Activity of Histatin-5 in Candida albicans.

Journal Article ACS infectious diseases · September 2022 Histatin-5 (Hist-5) is a polycationic, histidine-rich antimicrobial peptide with potent antifungal activity against the opportunistic fungal pathogen Candida albicans. Hist-5 can bind metals in vitro, and metals have been shown to alter the fungicid ... Full text Cite

Examination of diverse iron-chelating agents for the protection of differentiated PC12 cells against oxidative injury induced by 6-hydroxydopamine and dopamine.

Journal Article Scientific reports · June 2022 Labile redox-active iron ions have been implicated in various neurodegenerative disorders, including the Parkinson's disease (PD). Iron chelation has been successfully used in clinical practice to manage iron overload in diseases such as thalassemia major; ... Full text Cite

Prospective clinical trial of disulfiram plus copper in men with metastatic castration-resistant prostate cancer.

Journal Article Prostate · May 2022 BACKGROUND: In preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co-administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen-receptor signaling. However, prior trials of DSF in PC u ... Full text Link to item Cite

Connecting copper and cancer: from transition metal signalling to metalloplasia.

Journal Article Nature reviews. Cancer · February 2022 Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic re ... Full text Cite

Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli.

Journal Article Molecules (Basel, Switzerland) · September 2021 Pyrithione (2-mercaptopyridine-N-oxide) is a metal binding modified pyridine, the antibacterial activity of which was described over 60 years ago. The formulation of zinc-pyrithione is commonly used in the topical treatment of certain dermatological condit ... Full text Cite

Copper Availability Influences the Transcriptomic Response of Candida albicans to Fluconazole Stress.

Journal Article G3 (Bethesda, Md.) · April 2021 The ability of pathogens to maintain homeostatic levels of essential biometals is known to be important for survival and virulence in a host, which itself regulates metal availability as part of its response to infection. Given this importance of metal hom ... Full text Cite

Benzimidazole and Benzoxazole Zinc Chelators as Inhibitors of Metallo-β-Lactamase NDM-1.

Journal Article ChemMedChem · February 2021 Bacterial expression of β-lactamases, which hydrolyze β-lactam antibiotics, contributes to the growing threat of antibacterial drug resistance. Metallo-β-lactamases, such as NDM-1, use catalytic zinc ions in their active sites and hydrolyze nearly all clin ... Full text Cite

Single-Molecule Activation and Quantification of Mechanically Triggered Palladium-Carbene Bond Dissociation.

Journal Article Journal of the American Chemical Society · February 2021 Metal-complexed N-heterocyclic carbene (NHC) mechanophores are latent reactants and catalysts for a range of mechanically driven chemical responses, but mechanochemical scission of the metal-NHC bond has not been experimentally characterized. Here we repor ... Full text Cite

Protein Folding Stability Changes Across the Proteome Reveal Targets of Cu Toxicity in E. coli.

Journal Article ACS chemical biology · January 2021 The ability of metal ionophores to induce cellular metal hyperaccumulation endows them with potent antimicrobial activity; however, the targets and mechanisms behind these outcomes are not well understood. This work describes the first utilization of prote ... Full text Cite

Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans.

Journal Article Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · August 2020 Featured Publication Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compo ... Full text Cite

Dithiocarbamate prodrugs activated by prostate specific antigen to target prostate cancer.

Journal Article Bioorg Med Chem Lett · June 1, 2020 Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyld ... Full text Link to item Cite

A Cephalosporin Prochelator Inhibits New Delhi Metallo-β-lactamase 1 without Removing Zinc.

Journal Article ACS infectious diseases · May 2020 Featured Publication Antibacterial drug resistance is a rapidly growing clinical threat, partially due to expression of β-lactamase enzymes, which confer resistance to bacteria by hydrolyzing and inactivating β-lactam antibiotics. The increasing prevalence of metallo-β-lactama ... Full text Cite

A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis.

Journal Article Nature chemical biology · March 2020 Featured Publication Infection by the fungal pathogen Cryptococcus neoformans causes lethal meningitis, primarily in immune-compromised individuals. Colonization of the brain by C. neoformans is dependent on copper (Cu) acquisition from the host, which drives critical virulenc ... Full text Cite

Candida albicans reprioritizes metal handling during fluconazole stress.

Journal Article Metallomics : integrated biometal science · December 2019 Maintenance of metal homeostasis is critical to cell survival due to the multitude of cellular processes that depend on one or more metal cofactors. Here, we show that the opportunistic fungal pathogen Candida albicans extensively remodels its metal homeos ... Full text Cite

Histatin-5 interacts with cellular copper to promote antifungal activity against Candida albicans.

Journal Article Metallomics : integrated biometal science · December 2023 Histatin-5 (Hist-5) is an antimicrobial peptide found in human saliva that functions to defend the oral cavity from microbial infections, such as those caused by the fungal pathogen Candida albicans (C. albicans). Hist-5 can bind Cu in multiple oxidation s ... Full text Cite

Multiple Modes of Zinc Binding to Histatin 5 Revealed by Buffer-Independent Thermodynamics.

Journal Article Inorg Chem · May 8, 2023 Histatin 5 (Hist5) is an antimicrobial peptide found in human saliva as part of the innate immune system. Hist5 can bind several metal ions in vitro, and Zn2+ has been shown to function as an inhibitory switch to regulate the peptide's biological activity ... Full text Link to item Cite

Analysis of copper-induced protein precipitation across the E. coli proteome.

Journal Article Metallomics : integrated biometal science · January 2023 Metal cations have been exploited for their precipitation properties in a wide variety of studies, ranging from differentiating proteins from serum and blood to identifying the protein targets of drugs. Despite widespread recognition of this phenomenon, th ... Full text Cite

Intestinal mucin is a chaperone of multivalent copper.

Journal Article Cell · October 2022 Mucus protects the epithelial cells of the digestive and respiratory tracts from pathogens and other hazards. Progress in determining the molecular mechanisms of mucus barrier function has been limited by the lack of high-resolution structural information ... Full text Cite

Zinc Binding Inhibits Cellular Uptake and Antifungal Activity of Histatin-5 in Candida albicans.

Journal Article ACS infectious diseases · September 2022 Histatin-5 (Hist-5) is a polycationic, histidine-rich antimicrobial peptide with potent antifungal activity against the opportunistic fungal pathogen Candida albicans. Hist-5 can bind metals in vitro, and metals have been shown to alter the fungicid ... Full text Cite

Examination of diverse iron-chelating agents for the protection of differentiated PC12 cells against oxidative injury induced by 6-hydroxydopamine and dopamine.

Journal Article Scientific reports · June 2022 Labile redox-active iron ions have been implicated in various neurodegenerative disorders, including the Parkinson's disease (PD). Iron chelation has been successfully used in clinical practice to manage iron overload in diseases such as thalassemia major; ... Full text Cite

Prospective clinical trial of disulfiram plus copper in men with metastatic castration-resistant prostate cancer.

Journal Article Prostate · May 2022 BACKGROUND: In preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co-administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen-receptor signaling. However, prior trials of DSF in PC u ... Full text Link to item Cite

Connecting copper and cancer: from transition metal signalling to metalloplasia.

Journal Article Nature reviews. Cancer · February 2022 Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic re ... Full text Cite

Membrane Transporters Involved in the Antimicrobial Activities of Pyrithione in Escherichia coli.

Journal Article Molecules (Basel, Switzerland) · September 2021 Pyrithione (2-mercaptopyridine-N-oxide) is a metal binding modified pyridine, the antibacterial activity of which was described over 60 years ago. The formulation of zinc-pyrithione is commonly used in the topical treatment of certain dermatological condit ... Full text Cite

Copper Availability Influences the Transcriptomic Response of Candida albicans to Fluconazole Stress.

Journal Article G3 (Bethesda, Md.) · April 2021 The ability of pathogens to maintain homeostatic levels of essential biometals is known to be important for survival and virulence in a host, which itself regulates metal availability as part of its response to infection. Given this importance of metal hom ... Full text Cite

Benzimidazole and Benzoxazole Zinc Chelators as Inhibitors of Metallo-β-Lactamase NDM-1.

Journal Article ChemMedChem · February 2021 Bacterial expression of β-lactamases, which hydrolyze β-lactam antibiotics, contributes to the growing threat of antibacterial drug resistance. Metallo-β-lactamases, such as NDM-1, use catalytic zinc ions in their active sites and hydrolyze nearly all clin ... Full text Cite

Single-Molecule Activation and Quantification of Mechanically Triggered Palladium-Carbene Bond Dissociation.

Journal Article Journal of the American Chemical Society · February 2021 Metal-complexed N-heterocyclic carbene (NHC) mechanophores are latent reactants and catalysts for a range of mechanically driven chemical responses, but mechanochemical scission of the metal-NHC bond has not been experimentally characterized. Here we repor ... Full text Cite

Protein Folding Stability Changes Across the Proteome Reveal Targets of Cu Toxicity in E. coli.

Journal Article ACS chemical biology · January 2021 The ability of metal ionophores to induce cellular metal hyperaccumulation endows them with potent antimicrobial activity; however, the targets and mechanisms behind these outcomes are not well understood. This work describes the first utilization of prote ... Full text Cite

Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans.

Journal Article Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · August 2020 Featured Publication Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compo ... Full text Cite

Dithiocarbamate prodrugs activated by prostate specific antigen to target prostate cancer.

Journal Article Bioorg Med Chem Lett · June 1, 2020 Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyld ... Full text Link to item Cite

A Cephalosporin Prochelator Inhibits New Delhi Metallo-β-lactamase 1 without Removing Zinc.

Journal Article ACS infectious diseases · May 2020 Featured Publication Antibacterial drug resistance is a rapidly growing clinical threat, partially due to expression of β-lactamase enzymes, which confer resistance to bacteria by hydrolyzing and inactivating β-lactam antibiotics. The increasing prevalence of metallo-β-lactama ... Full text Cite

A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis.

Journal Article Nature chemical biology · March 2020 Featured Publication Infection by the fungal pathogen Cryptococcus neoformans causes lethal meningitis, primarily in immune-compromised individuals. Colonization of the brain by C. neoformans is dependent on copper (Cu) acquisition from the host, which drives critical virulenc ... Full text Cite

Candida albicans reprioritizes metal handling during fluconazole stress.

Journal Article Metallomics : integrated biometal science · December 2019 Maintenance of metal homeostasis is critical to cell survival due to the multitude of cellular processes that depend on one or more metal cofactors. Here, we show that the opportunistic fungal pathogen Candida albicans extensively remodels its metal homeos ... Full text Cite

Emerging Opportunities To Manipulate Metal Trafficking for Therapeutic Benefit.

Journal Article Inorganic chemistry · October 2019 The indispensable requirement for metals in life processes has led to the evolution of sophisticated mechanisms that allow organisms to maintain dynamic equilibria of these ions. This dynamic control of the level, speciation, and availability of a variety ... Full text Cite

Copper potentiates azole antifungal activity in a way that does not involve complex formation.

Journal Article Dalton transactions (Cambridge, England : 2003) · July 2019 To survive, fungal pathogens must acquire nutrient metals that are restricted by the host while also tolerating mechanisms of metal toxicity that are induced by the host. Given this dual vulnerability, we hypothesized that a pathogen's access to and contro ... Full text Cite

Metallomics: Emerging Investigators 2019.

Journal Article Metallomics : integrated biometal science · January 2019 Full text Cite

Introduction: Metals in Medicine.

Journal Article Chemical reviews · January 2019 Full text Cite

Modifying aroylhydrazone prochelators for hydrolytic stability and improved cytoprotection against oxidative stress.

Journal Article Bioorganic & medicinal chemistry · December 2018 BSIH ((E)-N'-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylidene)isonicotinohydrazide) is a prodrug version of the metal chelator SIH ((E)-N'-(2-hydroxybenzylidene)isonicotinohydrazide) in which a boronate group prevents metal chelation until react ... Full text Cite

Leveraging γ-Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells.

Journal Article Angew Chem Int Ed Engl · September 24, 2018 A prodrug approach is presented to direct copper-dependent cytotoxicity to prostate cancer cells. The prochelator GGTDTC requires activation by γ-glutamyl transferase (GGT) to release the metal chelator diethyldithiocarbamate from a linker that masks its t ... Full text Link to item Cite

Copper Influences the Antibacterial Outcomes of a β-Lactamase-Activated Prochelator against Drug-Resistant Bacteria.

Journal Article ACS Infect Dis · June 8, 2018 The unabated rise in bacterial resistance to conventional antibiotics, coupled with collateral damage to normal flora incurred by overuse of broad-spectrum antibiotics, necessitates the development of new antimicrobials targeted against pathogenic organism ... Full text Link to item Cite

Metal-binding hydrazone photoswitches for visible light reactivity and variable relaxation kinetics.

Journal Article Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · November 2017 The range of applications for photoswitching moieties is diverse, and the ability to design switches with variable photochemical and physical properties is consequently important for realizing their potential. Previously we reported on the photochromism of ... Full text Cite

The hydrolytic susceptibility of prochelator BSIH in aqueous solutions.

Journal Article Bioorganic & medicinal chemistry letters · September 2017 The prochelator BSIH ((E)-N'-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylidene)isonicotinohydrazide) contains a boronate group that prevents metal coordination until reaction with peroxide releases the iron chelator SIH ((E)-N'-(2-hydroxybenzylid ... Full text Cite

Specific Histidine Residues Confer Histatin Peptides with Copper-Dependent Activity against Candida albicans

Journal Article Biochemistry · August 1, 2017 The histidine-rich salivary peptides of the histatin family are known to bind copper (Cu) and other metal ions in vitro; however, the details of these interactions are poorly understood, and their implications for in vivo antifungal activity have not been ... Full text Open Access Link to item Cite

Chemical Approaches for Manipulating Microbial Metals

Conference JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY · July 1, 2017 Link to item Cite

Chemical and functional properties of metal chelators that mobilize copper to elicit fungal killing of Cryptococcus neoformans.

Journal Article Metallomics : integrated biometal science · January 2017 A panel of iron (Fe) and copper (Cu) chelators was screened for growth inhibitory activity against the fungal pathogen Cryptococcus neoformans. Select bidentate metal-binding ligands containing mixed O,S or O,N donor atoms were identified as agents that in ... Full text Cite

Stimulus-Responsive Prochelators for Manipulating Cellular Metals.

Journal Article Accounts of chemical research · November 2016 Metal ions are essential for a wide range of physiological processes, but they can also be toxic if not appropriately regulated by a complex network of metal trafficking proteins. Intervention in cellular metal distribution with small-molecule or peptide c ... Full text Cite

Novel aminoalkyl tris-cyclometalated iridium complexes as cellular stains.

Journal Article Dalton transactions (Cambridge, England : 2003) · November 2016 Herein we report the synthesis and investigation of the properties of two tris-cyclometalated luminescent iridium complexes. These complexes are the simple derivatives of fac-[Ir(ppy)3] bearing amino alkyl groups on one of the phenylpyridine rin ... Full text Cite

Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury.

Journal Article Toxicology · September 2016 Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and d ... Full text Cite

Characterization of cytoprotective and toxic properties of iron chelator SIH, prochelator BSIH and their degradation products.

Journal Article Toxicology · March 2016 Free cellular iron catalyzes the formation of toxic hydroxyl radicals and therefore chelation of iron could be a promising therapeutic approach in pathological states associated with oxidative stress. Salicylaldehyde isonicotinoyl hydrazone (SIH) is a stro ... Full text Cite

A multifunctional, light-activated prochelator inhibits UVA-induced oxidative stress.

Journal Article Bioorganic & medicinal chemistry letters · November 2015 UVA radiation can damage cells and tissues by direct photodamage of biomolecules as well as by initiating metal-catalyzed oxidative stress. In order to alleviate both concerns simultaneously, we synthesized a multifunctional prochelator PC-HAPI (2-((E)-1-( ... Full text Cite

Model Peptide Studies Reveal a Mixed Histidine-Methionine Cu(I) Binding Site at the N-Terminus of Human Copper Transporter 1.

Journal Article Inorganic chemistry · September 2015 Copper is a vital metal cofactor in enzymes that are essential to myriad biological processes. Cellular acquisition of copper is primarily accomplished through the Ctr family of plasma membrane copper transport proteins. Model peptide studies indicate that ... Full text Cite

A prochelator peptide designed to use heterometallic cooperativity to enhance metal ion affinity.

Journal Article Chemical science · June 2015 A peptide has been designed so that its chelating affinity for one type of metal ion regulates its affinity for a second, different type of metal ion. The prochelator peptide (PCP), which is a fusion of motifs evocative of calcium loops and zinc fingers, f ... Full text Cite

Preface. Biometals 2014--Proceedings of the 9th International Symposium Biometals 2014 at Duke University, Durham, NC, USA.

Journal Article Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · June 2015 Full text Cite

Pharmacological activity of metal binding agents that alter copper bioavailability.

Journal Article Dalton transactions (Cambridge, England : 2003) · May 2015 Iron, copper and zinc are required nutrients for many organisms but also potent toxins if misappropriated. An overload of any of these metals can be cytotoxic and ultimately lead to organ failure, whereas deficiencies can result in anemia, weakened immune ... Full text Cite

LC-UV/MS methods for the analysis of prochelator-boronyl salicylaldehyde isonicotinoyl hydrazone (BSIH) and its active chelator salicylaldehyde isonicotinoyl hydrazone (SIH).

Journal Article Journal of pharmaceutical and biomedical analysis · February 2015 Salicylaldehyde isonicotinoyl hydrazone (SIH) is an intracellular iron chelator with well documented potential to protect against oxidative injury both in vitro and in vivo. However, it suffers from short biological half-life caused by fast hydrolysis of t ... Full text Cite

Copper signaling axis as a target for prostate cancer therapeutics.

Journal Article Cancer Res · October 15, 2014 Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for pro ... Full text Open Access Link to item Cite

A prochelator with a modular masking group featuring hydrogen peroxide activation with concurrent fluorescent reporting.

Journal Article Chemical communications (Cambridge, England) · October 2014 Metal chelators masked with protecting groups for targeted release have the potential to conditionally modulate cellular metals. We report a new route to prepare cis-cinnamate protecting groups that enabled development of a prochelator with chemical stimul ... Full text Cite

Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury.

Journal Article Free radical biology & medicine · September 2014 Oxidative stress is a common denominator of numerous cardiovascular disorders. Free cellular iron catalyzes the formation of highly toxic hydroxyl radicals, and iron chelation may thus be an effective therapeutic approach. However, using classical iron che ... Full text Cite

Exploiting innate immune cell activation of a copper-dependent antimicrobial agent during infection.

Journal Article Chemistry & biology · August 2014 Recalcitrant microbial infections demand new therapeutic options. Here we present an approach that exploits two prongs of the host immune cell antimicrobial response: the oxidative burst and the compartmentalization of copper (Cu) within phagolysosomes. Th ... Full text Cite

Detection of Metal Ions, Anions and Small Molecules Using Metal Complexes

Chapter · June 23, 2014 A chemical sensor reports the presence of an analyte by converting a recognition event into a spectroscopic signal. Currently used sensors largely rely on organic dyes, fluorescent bteins, nanoparticles, and metal complexes for responsive signal transducti ... Full text Cite

Manipulating metals at the host-pathogen interface

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 16, 2014 Link to item Cite

Characterization of a photoswitching chelator with light-modulated geometric, electronic, and metal-binding properties.

Journal Article Inorganic chemistry · February 2014 Photoswitching molecules are utilized for a variety of applications where the rapid manipulation of the molecules' chemical properties and spatial orientations allows for new spatiotemporal control over molecular-scale interactions and processes. Here, we ... Full text Cite

Development of stimulus-responsive metal chelation with novel fluorescence reporting

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · April 7, 2013 Link to item Cite

Clawing back: broadening the notion of metal chelators in medicine.

Journal Article Current opinion in chemical biology · April 2013 The traditional notion of chelation therapy is the administration of a chemical agent to remove metals from the body. But formation of a metal-chelate can have biological ramifications that are much broader than metal elimination. Exploring these other pos ... Full text Cite

Light uncages a copper complex to induce nonapoptotic cell death.

Journal Article Chemical communications (Cambridge, England) · March 2013 Cu3G is a Cu(II) complex of a photoactive tetradentate ligand that is cleaved upon UV irradiation to release Cu. Here we show that the cytotoxicity of Cu3G increases in response to brief UV stimulation to result in extensive cytoplasmic vacuolization that ... Full text Cite

Bioinorganic Neurochemistry

Journal Article · January 1, 2013 Sodium, potassium, and calcium are, in many respects, the cornerstones of neuronal signaling, but d-block metal ions also play important roles in brain function. The brain has unique needs for metalloenzymes that use iron, zinc, copper, and manganese, and ... Full text Cite

A boronate prochelator built on a triazole framework for peroxide-triggered tridentate metal binding.

Journal Article Inorganica chimica acta · December 2012 Iron chelating agents have the potential to minimize damage associated with oxidative stress in a range of diseases; however, this potential is countered by risks of indiscriminant metal binding or iron depletion in conditions not associated with systemic ... Full text Cite

Probing oxidative stress: Small molecule fluorescent sensors of metal ions, reactive oxygen species, and thiols.

Journal Article Coordination chemistry reviews · October 2012 Oxidative stress is a common feature shared by many diseases, including neurodegenerative diseases. Factors that contribute to cellular oxidative stress include elevated levels of reactive oxygen species, diminished availability of detoxifying thiols, and ... Full text Cite

Monitoring β-secretase activity in living cells with a membrane-anchored FRET probe.

Journal Article Angewandte Chemie (International ed. in English) · October 2012 Full text Cite

Prochelator BHAPI protects cells against paraquat-induced damage by ROS-triggered iron chelation.

Journal Article Metallomics : integrated biometal science · August 2012 A prochelator named BHAPI (N'-(1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyloxy)phenyl)ethylidene)isonicotinohydrazide) based on the structure of experimental metal chelator HAPI (N'-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide) has b ... Full text Cite

Application of inorganic chemistry for non-cancer therapeutics.

Journal Article Dalton transactions (Cambridge, England : 2003) · June 2012 Full text Cite

Optimizing prochelators to bind metal ions in response to disease-associated stimuli[p]

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 25, 2012 Link to item Cite

BACE activated prochelator mediates A beta-Cu toxicity in an Alzheimer's disease cell model

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 25, 2012 Link to item Cite

Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function.

Journal Article Journal of inorganic biochemistry · February 2012 Biological copper is coordinated predominantly by just three ligand types: the side chains of histidine, cysteine, and methionine, with of course some exceptions. The arrangement of these components, however, is fascinating. The diversity provided by just ... Full text Cite

A Cell-Permeable Fluorescent Prochelator Responds to Hydrogen Peroxide and Metal Ions by Decreasing Fluorescence.

Journal Article Inorganica chimica acta · January 2012 Described here is the development of two boronic ester-based fluorescent prochelators, FloB (2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-4(5)-[2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene-hydrazinocarbonyl]-benzoic acid) and FloB-SI (2-(6-hydroxy-3 ... Full text Cite

Prochelators triggered by hydrogen peroxide provide hexadentate iron coordination to impede oxidative stress.

Journal Article Journal of inorganic biochemistry · September 2011 Prochelators are agents that have little affinity for metal ions until they undergo a chemical conversion. Three new aryl boronate prochelators are presented that are responsive to hydrogen peroxide to provide hexadentate ligands for chelating metal ions. ... Full text Cite

Design of prochelators that bind cellular metal ions in response to diverse stimuli

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 28, 2011 Link to item Cite

Model peptides provide new insights into the role of histidine residues as potential ligands in human cellular copper acquisition via Ctr1.

Journal Article Journal of the American Chemical Society · March 2011 Cellular acquisition of copper in eukaryotes is primarily accomplished through the Ctr family of copper transport proteins. In both humans and yeast, methionine-rich "Mets" motifs in the amino-terminal extracellular domain of Ctr1 are thought to be respons ... Full text Cite

Keys for unlocking photolabile metal-containing cages.

Journal Article Angewandte Chemie (International ed. in English) · January 2011 Photolabile metal-containing cages are metal complexes that undergo a change in coordination environment upon exposure to light of an appropriate wavelength. The light-responsive functionality can either be a component of the encapsulating ligand or a prop ... Full text Cite

A comparison of methionine, histidine and cysteine in copper(I)-binding peptides reveals differences relevant to copper uptake by organisms in diverse environments.

Journal Article Metallomics : integrated biometal science · January 2011 The N-terminal, extracellular regions of eukaryotic high affinity copper transport (Ctr) proteins vary in composition of the Cu(i) binding amino acids: methionine, histidine, and cysteine. To examine why certain amino acids are exploited over others in Ctr ... Cite

A comparison of methionine, histidine and cysteine in copper(I)-binding peptides reveals differences relevant to copper uptake by organisms in diverse environments.

Journal Article Metallomics : integrated biometal science · January 2011 The N-terminal, extracellular regions of eukaryotic high affinity copper transport (Ctr) proteins vary in composition of the Cu(i) binding amino acids: methionine, histidine, and cysteine. To examine why certain amino acids are exploited over others in Ctr ... Full text Cite

Development of next-generation photolabile copper cages with improved copper binding properties.

Journal Article Dalton transactions (Cambridge, England : 2003) · October 2010 Seven new nitrogen-donor ligands that contain a photoactive nitrophenyl group within the ligand backbone have been prepared and evaluated for their binding affinity for copper(ii) and zinc(ii). Among this series, the ligand 3Gcage (pyridine-2-carboxylic ac ... Full text Open Access Cite

Methionine motifs of copper transport proteins provide general and flexible thioether-only binding sites for Cu(I) and Ag(I).

Journal Article Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · September 2010 Cellular acquisition of copper in eukaryotic organisms is primarily accomplished through high-affinity copper transport proteins (Ctr). The extracellular N-terminal regions of both human and yeast Ctr1 contain multiple methionine residues organized in copp ... Full text Cite

Insights into the role of histidine in Ctr1-dependent copper uptake

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 22, 2010 Link to item Cite

Development of triggereable chelating agents as probes for metal-induced oxidative stress

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 22, 2010 Link to item Cite

The highways and byways of bioinorganic chemistry.

Journal Article Current opinion in chemical biology · April 2010 Full text Cite

A prochelator activated by beta-secretase inhibits Abeta aggregation and suppresses copper-induced reactive oxygen species formation.

Journal Article Journal of the American Chemical Society · April 2010 The intersection of the amyloid cascade hypothesis and the implication of metal ions in Alzheimer's disease progression has sparked an interest in using metal-binding compounds as potential therapeutic agents. In the present work, we describe a prochelator ... Full text Open Access Cite

Minding metals: tailoring multifunctional chelating agents for neurodegenerative disease.

Journal Article Dalton transactions (Cambridge, England : 2003) · March 2010 Neurodegenerative diseases like Alzheimer's and Parkinson's disease are associated with elevated levels of iron, copper, and zinc and consequentially high levels of oxidative stress. Given the multifactorial nature of these diseases, it is becoming evident ... Full text Open Access Cite

Electronic structure of a paramagnetic {MNO}6 complex: MnNO 5,5-tropocoronand.

Journal Article Inorganic chemistry · March 2010 Using density functional theory (OLYP/STO-TZP) calculations, we have investigated the electronic structure of [Mn(5,5-tropocoronand)(NO)], a rare paramagnetic {MNO}(6) complex. Experimental methods, including magnetic susceptibility measurements and high-f ... Full text Cite

Toward the development of prochelators as fluorescent probes of copper-mediated oxidative stress.

Journal Article Dalton transactions (Cambridge, England : 2003) · January 2010 A fluorescent sensor prochelator, FlamB (fluorescein hydrizido 2-imidophenylboronic ester), has been developed that selectively probes for copper under conditions of oxidative stress. High levels of hydrogen peroxide trigger the release of a boronic ester ... Full text Cite

A prochelator activated by hydrogen peroxide prevents metal-induced amyloid Beta aggregation.

Journal Article Chembiochem : a European journal of chemical biology · January 2010 Full text Cite

A photo-caged platinum(II) complex that increases cytotoxicity upon light activation

Journal Article European Journal of Inorganic Chemistry · January 1, 2010 A novel platinum(II) photocaged complex called [Pt(cage)] has been prepared and characterized by X-ray crystallography. The complex contains a photolabile nitrophenyl group incorporated into the backbone of a tetradentate ligand that contains two pyridyl a ... Full text Cite

Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.

Journal Article Metallomics : integrated biometal science · January 2010 Platinum therapeutic agents are widely used in the treatment of several forms of cancer. Various mechanisms for the transport of the drugs have been proposed including passive diffusion across the cellular membrane and active transport via proteins. The co ... Full text Open Access Cite

Introduction to "cellular metal homeostasis and trafficking".

Journal Article Chemical reviews · October 2009 Full text Cite

Characterization of thioether-only Cu(I) binding by Ctr1 methionine motifs

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 16, 2009 Link to item Cite

Synthesis of masked bidentate and hexadentate iron chelators designed to reduce oxidative stress

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 16, 2009 Link to item Cite

Spectroscopic studies of N-terminal Cu(II)- and Cu(I)-binding hCtrl model peptides

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 16, 2009 Link to item Cite

Design of triggerable ligands for altering metal coordination in biological settings

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 16, 2009 Link to item Cite

Photolabile ligand for light-activated release of caged copper

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 22, 2009 Link to item Cite

Iron prochelator BSIH protects retinal pigment epithelial cells against cell death induced by hydrogen peroxide.

Journal Article Journal of inorganic biochemistry · December 2008 Dysregulation of localized iron homeostasis is implicated in several degenerative diseases, including Parkinson's, Alzheimer's, and age-related macular degeneration, wherein iron-mediated oxidative stress is hypothesized to contribute to cell death. Inhibi ... Full text Cite

A photolabile ligand for light-activated release of caged copper.

Journal Article Journal of the American Chemical Society · September 2008 A photosensitive caged copper complex has been prepared from a tetradentate ligand (H2cage) composed of two pyridyl-amide arms connected by a photoreactive nitrophenyl group. H2cage binds Cu2+ in aqueous solution with a stability constant (log beta) of 10. ... Full text Cite

INOR 273-Development of prochelators as probes of iron-induced oxidative stress

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · April 6, 2008 Link to item Cite

Copper shares a piece of the pi.

Journal Article Nature chemical biology · February 2008 Full text Cite

Counterions influence reactivity of metal ions with cysteinyldopa model compounds.

Journal Article Inorganic chemistry · February 2008 Cysteinyldopas are naturally occurring conjugates of cysteine and dopa (3,4-dihydroxy-l-phenylalanine) that are precursors to red pheomelanin pigments. Metal ions are known to influence pheomelanogenesis in vitro and may be regulatory factors in vivo. Cydo ... Full text Cite

Modifications of boronic ester pro-chelators triggered by hydrogen peroxide tune reactivity to inhibit metal-promoted oxidative stress.

Journal Article Dalton transactions (Cambridge, England : 2003) · November 2007 Several new analogs of salicylaldehyde isonicotinoyl hydrazone (SIH) and salicylaldehyde benzoyl hydrazone (SBH) that contain an aryl boronic ester (BSIH, BSBH) or acid (BASIH) in place of an aryl hydroxide have been synthesized and characterized as masked ... Full text Cite

INOR 916-A pro-chelator strategy for inhibiting metal-catalyzed oxidative stress

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 19, 2007 Link to item Cite

Phosphorylation-dependent metal binding by alpha-synuclein peptide fragments.

Journal Article Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · February 2007 Alpha-synuclein (alpha-syn) is the major protein component of the insoluble fibrils that make up Lewy bodies, the hallmark lesions of Parkinson's disease. Its C-terminal region contains motifs of charged amino acids that potentially bind metal ions, as wel ... Full text Cite

INOR 614-Development of iron chelators triggered by reactive oxygen species

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · September 10, 2006 Link to item Cite

INOR 1011-Copper(I) binding by methionine-rich domains of copper transport proteins

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · September 10, 2006 Link to item Cite

A pro-chelator triggered by hydrogen peroxide inhibits iron-promoted hydroxyl radical formation.

Journal Article Journal of the American Chemical Society · September 2006 The synthesis and structural characterization of a new pro-chelating agent, isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]-hydrazide (BSIH), are presented. BSIH only weakly interacts with iron unless hydrogen peroxide (H2O ... Full text Cite

Synthesis and characterization of copper(II) complexes of cysteinyldopa and benzothiazine model ligands related to pheomelanin.

Journal Article Inorganic chemistry · August 2006 A new cysteinyldopa model ligand Cydo {3-[(2-aminoethyl)sulfanyl]-4,6-di-tert-butylbenzene-1,2-diol} was prepared and its reactivity with Cu(II) explored. Under anaerobic conditions, tetranuclear [Cu4(Cydo)4] is isolated, but in the presence of O2, a benzo ... Full text Cite

Fe(III)-coordination properties of neuromelanin components: 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid.

Journal Article Inorganic chemistry · May 2006 The Fe(III)-coordination chemistry of neuromelanin building-block compounds, 5,6-dihydroxyindole (DHI), 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and 5,6-dihydroxy-N-methyl-indole (Me-DHI), and the neurotransmitter dopamine were explored in aqueous so ... Full text Cite

A Mets motif peptide found in copper transport proteins selectively binds Cu(I) with methionine-only coordination.

Journal Article Inorganic chemistry · December 2005 Mets motifs, which refer to methionine-rich sequences found in the high-affinity copper transporter Ctr1, also appear in other proteins involved in copper trafficking and homeostasis, including other Ctrs as well as Pco and Cop proteins isolated from coppe ... Full text Cite

Phosphorylation of an alpha-synuclein peptide fragment enhances metal binding.

Journal Article Journal of the American Chemical Society · July 2005 By using Tb3+ as a luminescent probe, we demonstrate that the phosphorylation state of a 14-residue peptide fragment of alpha-synuclein, a protein implicated in Parkinson's Disease, dramatically affects the metal ion affinity of the peptide. Whereas the un ... Full text Cite

Characterization of metal binding sites in a synthetic phosphorylated alpha-synuclein peptide fragment.

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 13, 2005 Link to item Cite

Structural origin of the high affinity of a chemically evolved lanthanide-binding peptide.

Journal Article Angewandte Chemie (International ed. in English) · July 2004 Full text Cite

Protein alignment by a coexpressed lanthanide-binding tag for the measurement of residual dipolar couplings.

Journal Article Journal of the American Chemical Society · November 2003 A protein fusion construct of human ubiquitin with an N-terminal lanthanide binding tag (LBT) enables observation of long-range orientational restraints in solution NMR from residual dipolar couplings (RDCs) due to paramagnetic alignment of the protein. Th ... Full text Cite

Lanthanide-binding tags as versatile protein coexpression probes.

Journal Article Chembiochem : a European journal of chemical biology · April 2003 Comprehensive proteomic analyses require new methodologies to accelerate the correlation of gene sequence with protein function. Key tools for such efforts include biophysical probes that integrate into the covalent architecture of proteins. Lanthanide-bin ... Full text Cite

A powerful combinatorial screen to identify high-affinity terbium(III)-binding peptides.

Journal Article Chembiochem : a European journal of chemical biology · April 2003 Lanthanide-binding tags (LBTs) are protein fusion partners consisting of encoded amino acids that bind lanthanide ions with high affinity. Herein, we present a new screening methodology for the identification of new LBT sequences with high affinity for Tb( ... Full text Cite

Pentacoordinate cobalt(III) thiolate and nitrosyl tropocoronand compounds.

Journal Article Inorganic chemistry · July 2001 Reaction of [Co(TC-n,m)]+ with (Me4N)(SC6F5), where (TC-n,m) is a tropocoronand with n and m linker chain methylene groups, yielded the thiolate complexes [Co(SC6F5)(TC-3,3)] (1a), and [Co(SC6F5)(TC-4,4)] (2a), which were structurally characterized. Use of ... Full text Cite

Aminotroponiminates as ligands for potential metal-based nitric oxide sensors.

Journal Article Inorganic chemistry · September 2000 A family of new fluorescently labeled ligands, HRDATI, was prepared to develop transition-metal-based NO sensing strategies. The ligands are composed of aminotroponiminates (ATIs) with a dansyl fluorophore on one of the imine nitrogen atoms and an alkyl su ... Full text Cite

Metal-based NO sensing by selective ligand dissociation

Journal Article Angewandte Chemie - International Edition · 2000 Nitric oxide reacts selectively with the O2 stable, weakly fluorescent complex [Co(DATI-4)] in dichloromethane solution to dissociate a fluorophore- substituted arm of the aminotroponiminate ligand DATI-4. The resulting cobalt-dinitrosyl adduct (see pictur ... Full text Cite

NO disproportionation reactivity of Fe tropocoronand complexes

Journal Article Journal of the American Chemical Society · November 17, 1999 The synthesis and characterization of divalent [Fe(TC-5,5)] (1) and trivalent [Fe(OTf)(TC-5,5)] (2) tropocoronand complexes are described. Compound 1 reacts with 1 equiv of NO to form the {FeNO}7 complex 3. A single-crystal X-ray structure determination of ... Full text Cite

Disproportionation of nitric oxide promoted by a Mn tropocoronand

Journal Article Chemtracts · February 1, 1999 Cite

Supramolecular Alcohol-Amine Crystals and Their Hydrogen-Bond Patterns

Journal Article Acta Crystallographica Section B: Structural Science · October 1, 1998 An analysis of the structures of five new cocrystals with saturated hydrogen bonding between amines and alcohols is presented. These five are all cocrystals with p-phenylenediamine (PDA) and a mono- or diol. The cocrystals are p-phenylenediamine-phenol (1/ ... Full text Cite

Disproportionation of nitric oxide promoted by a Mn tropocoronand

Journal Article Journal of the American Chemical Society · September 9, 1998 The synthesis and characterization of the divalent tropocoronand, [Mn(THF)(TC-5,5)] (1), are described. Compound 1 reacts with NO to afford a discrete mononitrosyl [Mn(NO)(TC-5,5)] (2), which was isolated and shown formally to contain the {Mn(III)NO-}2+ fr ... Full text Cite

Polymer pendant ligand chemistry-5. The selective and competitive removal of Ag+, Hg2+, Cu2+, Pb2+ and Cd2+ ions from aqueous solution utilizing a N-sulfonylethylenebis(dithiocarbamate) ligand anchored on macroporous polystyrene-divinylbenzene beads

Journal Article Polyhedron · September 6, 1996 An important new focus for environmental inorganic chemistry is the selective removal and recovery of metal ions from aqueous solution with organic ligands anchored to modified polymer backbones. Several significant criteria for facile metal ion removal fr ... Full text Cite

Polymer Pendant Ligand Chemistry. 3. A Biomimetic Approach to Selective Metal Ion Removal and Recovery from Aqueous Solution with Polymer-Supported Sulfonated Catechol and Linear Catechol Amide Ligands

Journal Article Inorganic Chemistry · May 1, 1995 The design of organic ligands to selectively remove and recover metal ions from aqueous solution is a new and important area of environmental inorganic chemistry. One approach to designing organic ligands for these purposes is to use biological systems as ... Full text Cite

Synthetic and Structural Studies of a Linear Bis-Catechol Amide, N,N′-Bis(2,3-dihydroxybenzoyl)-1,7-diazaheptane (5-LICAM), and Its Complexes with Ni2+ and Co2+: Utilization of a Polymer-Supported, Sulfonated Analog, 5-LICAMS, as a Biomimetic Ligand for Divalent Metal Ion Removal from Aqueous Solution

Journal Article Inorganic Chemistry · May 1, 1995 The synthesis and structural characterization of the linear bis(catechol) amide ligand, N,N’-bis(2,3-dihydroxybenzoyl)-l,7-diazaheptane (5-LICAM, 1), was studied along with several metal complexes, namely, Ni2+ and Co2+. We were able to obtain a single-cry ... Full text Cite