Scholars@Duke
Dewey G. McCafferty

Dewey G. McCafferty

Professor of Chemistry
Chemistry
dewey.mccafferty@duke.edu
Box 90346, B120 LSRC Bldg, Dept. Chemistry, Durham, NC 27708-0346
B120 LSRC, Box 90346, 450 Research Drive, Dept. Chemistry, Durham, NC 27708-0346
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Selected Publications

Chemoproteomic-enabled characterization of small GTPase Rab1a as a target of an N-arylbenzimidazole ligand's rescue of Parkinson's-associated cell toxicity.

Journal Article RSC chemical biology · January 2022 The development of phenotypic models of Parkinson's disease (PD) has enabled screening and identification of phenotypically active small molecules that restore complex biological pathways affected by PD toxicity. While these phenotypic screening platforms ... Full text Cite

Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.

Journal Article FEBS letters · December 2021 Chlamydia trachomatis, an obligate intracellular bacterium with limited metabolic capabilities, possesses the futalosine pathway for menaquinone biosynthesis. Futalosine pathway enzymes have promise as narrow-spectrum antibiotic targets, but the activity a ... Full text Open Access Cite

Small Molecule Improvement of Trafficking Defects in Models of Neurodegeneration.

Journal Article ACS chemical neuroscience · November 2021 Disrupted cellular trafficking and transport processes are hallmarks of many neurodegenerative disorders (NDs). Recently, efforts have been made toward developing and implementing experimental platforms to identify small molecules that may help restore nor ... Full text Cite

Discovery of the Class I Antimicrobial Lasso Peptide Arcumycin.

Journal Article Chembiochem : a European journal of chemical biology · August 2021 Lasso peptides are a structurally diverse superfamily of conformationally constrained peptide natural products, of which a subset exhibits broad antimicrobial activity. Although advances in bioinformatics have increased our knowledge of strains harboring t ... Full text Cite

Characterization of Small-Molecule-Induced Changes in Parkinson's-Related Trafficking via the Nedd4 Ubiquitin Signaling Cascade.

Journal Article Cell Chem Biol · January 21, 2021 The benzdiimidazole NAB2 rescues α-synuclein-associated trafficking defects associated with early onset Parkinson's disease in a Nedd4-dependent manner. Despite identification of E3 ubiquitin ligase Nedd4 as a putative target of NAB2, its molecular mechani ... Full text Link to item Cite

Discovery of Six Ramoplanin Family Gene Clusters and the Lipoglycodepsipeptide Chersinamycin*.

Journal Article Chembiochem : a European journal of chemical biology · January 2021 Featured Publication Ramoplanins and enduracidins are peptidoglycan lipid intermediate II-binding lipodepsipeptides with broad-spectrum activity against methicillin- and vancomycin-resistant Gram-positive pathogens. Targeted genome mining using probes from conserved sequences ... Full text Cite

Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.

Journal Article PloS one · January 2021 The Nedd4 family contains several structurally related but functionally distinct HECT-type ubiquitin ligases. The members of the Nedd4 family are known to recognize substrates through their multiple WW domains, which recognize PY motifs (PPxY, LPxY) or pho ... Full text Cite

Robust and facile purification of full-length, untagged human Nedd4 as a recombinant protein from Escherichia coli.

Journal Article Protein expression and purification · September 2020 Featured Publication Nedd4 is an E3 ubiquitin ligase that has received increased attention due to its role in the maintenance of proteostasis and in cellular stress responses. Investigation of Nedd4 enzymology has revealed a complex enzymatic mechanism that involves intermolec ... Full text Cite

Insights into the Autoproteolytic Processing and Catalytic Mechanism of the Chlamydia trachomatis Virulence-Associated Protease CPAF.

Journal Article Biochemistry · August 20, 2019 Featured Publication CPAF (chlamydial protease-like activity factor) is a Chlamydia trachomatis protease that is translocated into the host cytosol during infection. CPAF activity results in dampened host inflammation signaling, cytoskeletal remodeling, and suppressed neutroph ... Full text Link to item Cite

Identification of Protease Specificity by Combining Proteome-Derived Peptide Libraries and Quantitative Proteomics.

Journal Article Molecular & cellular proteomics : MCP · July 2016 We present protease specificity profiling based on quantitative proteomics in combination with proteome-derived peptide libraries. Peptide libraries are generated by endoproteolytic digestion of proteomes without chemical modification of primary amines bef ... Full text Cite

Lysine-Specific Demethylase 1A (KDM1A/LSD1): Product Recognition and Kinetic Analysis of Full-Length Histones.

Journal Article Biochemistry · March 2016 Lysine-specific demethylase 1A (KDM1A/LSD1) is a FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively. Although the active site is expanded compared to that ... Full text Cite

The Chlamydia trachomatis Protease CPAF Contains a Cryptic PDZ-Like Domain with Similarity to Human Cell Polarity and Tight Junction PDZ-Containing Proteins.

Journal Article PLoS One · 2016 The need for more effective anti-chlamydial therapeutics has sparked research efforts geared toward further understanding chlamydial pathogenesis mechanisms. Recent studies have implicated the secreted chlamydial serine protease, chlamydial protease-like a ... Full text Link to item Cite

A rationally-designed chimeric KDM1A/KDM1B histone demethylase tower domain deletion mutant retaining enzymatic activity.

Journal Article FEBS letters · August 2015 A target with therapeutic potential, lysine-specific demethylase 1A (KDM1A) is a regulator of gene expression whose tower domain is a protein-protein interaction motif. This domain facilitates the interaction of KDM1A with coregulators and multiprotein com ... Full text Cite

KDM1 class flavin-dependent protein lysine demethylases.

Journal Article Biopolymers · July 2015 Flavin-dependent, lysine-specific protein demethylases (KDM1s) are a subfamily of amine oxidases that catalyze the selective posttranslational oxidative demethylation of methyllysine side chains within protein and peptide substrates. KDM1s participate in t ... Full text Cite

Reassessing the role of the secreted protease CPAF in Chlamydia trachomatis infection through genetic approaches.

Journal Article Pathog Dis · August 2014 The secreted Chlamydia protease CPAF cleaves a defined set of mammalian and Chlamydia proteins in vitro. As a result, this protease has been proposed to modulate a range of bacterial and host cellular functions. However, it has recently come into question ... Full text Link to item Cite

Sortases

Journal Article · August 29, 2013 Full text Cite

Sortase-catalyzed initiator attachment enables high yield growth of a stealth polymer from the C terminus of a protein.

Journal Article Macromolecular rapid communications · August 2013 Conventional methods for synthesizing protein/peptide-polymer conjugates, as a means to improve the pharmacological properties of therapeutic biomolecules, typically have drawbacks including low yield, non-trivial separation of conjugates from reactants, a ... 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

Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners.

Journal Article ACS Chem Biol · July 20, 2012 Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those contain ... Full text Link to item Cite

Chemoproteomic-enabled characterization of small GTPase Rab1a as a target of an N-arylbenzimidazole ligand's rescue of Parkinson's-associated cell toxicity.

Journal Article RSC chemical biology · January 2022 The development of phenotypic models of Parkinson's disease (PD) has enabled screening and identification of phenotypically active small molecules that restore complex biological pathways affected by PD toxicity. While these phenotypic screening platforms ... Full text Cite

Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.

Journal Article FEBS letters · December 2021 Chlamydia trachomatis, an obligate intracellular bacterium with limited metabolic capabilities, possesses the futalosine pathway for menaquinone biosynthesis. Futalosine pathway enzymes have promise as narrow-spectrum antibiotic targets, but the activity a ... Full text Open Access Cite

Small Molecule Improvement of Trafficking Defects in Models of Neurodegeneration.

Journal Article ACS chemical neuroscience · November 2021 Disrupted cellular trafficking and transport processes are hallmarks of many neurodegenerative disorders (NDs). Recently, efforts have been made toward developing and implementing experimental platforms to identify small molecules that may help restore nor ... Full text Cite

Discovery of the Class I Antimicrobial Lasso Peptide Arcumycin.

Journal Article Chembiochem : a European journal of chemical biology · August 2021 Lasso peptides are a structurally diverse superfamily of conformationally constrained peptide natural products, of which a subset exhibits broad antimicrobial activity. Although advances in bioinformatics have increased our knowledge of strains harboring t ... Full text Cite

Characterization of Small-Molecule-Induced Changes in Parkinson's-Related Trafficking via the Nedd4 Ubiquitin Signaling Cascade.

Journal Article Cell Chem Biol · January 21, 2021 The benzdiimidazole NAB2 rescues α-synuclein-associated trafficking defects associated with early onset Parkinson's disease in a Nedd4-dependent manner. Despite identification of E3 ubiquitin ligase Nedd4 as a putative target of NAB2, its molecular mechani ... Full text Link to item Cite

Discovery of Six Ramoplanin Family Gene Clusters and the Lipoglycodepsipeptide Chersinamycin*.

Journal Article Chembiochem : a European journal of chemical biology · January 2021 Featured Publication Ramoplanins and enduracidins are peptidoglycan lipid intermediate II-binding lipodepsipeptides with broad-spectrum activity against methicillin- and vancomycin-resistant Gram-positive pathogens. Targeted genome mining using probes from conserved sequences ... Full text Cite

Predicting PY motif-mediated protein-protein interactions in the Nedd4 family of ubiquitin ligases.

Journal Article PloS one · January 2021 The Nedd4 family contains several structurally related but functionally distinct HECT-type ubiquitin ligases. The members of the Nedd4 family are known to recognize substrates through their multiple WW domains, which recognize PY motifs (PPxY, LPxY) or pho ... Full text Cite

Robust and facile purification of full-length, untagged human Nedd4 as a recombinant protein from Escherichia coli.

Journal Article Protein expression and purification · September 2020 Featured Publication Nedd4 is an E3 ubiquitin ligase that has received increased attention due to its role in the maintenance of proteostasis and in cellular stress responses. Investigation of Nedd4 enzymology has revealed a complex enzymatic mechanism that involves intermolec ... Full text Cite

Insights into the Autoproteolytic Processing and Catalytic Mechanism of the Chlamydia trachomatis Virulence-Associated Protease CPAF.

Journal Article Biochemistry · August 20, 2019 Featured Publication CPAF (chlamydial protease-like activity factor) is a Chlamydia trachomatis protease that is translocated into the host cytosol during infection. CPAF activity results in dampened host inflammation signaling, cytoskeletal remodeling, and suppressed neutroph ... Full text Link to item Cite

Identification of Protease Specificity by Combining Proteome-Derived Peptide Libraries and Quantitative Proteomics.

Journal Article Molecular & cellular proteomics : MCP · July 2016 We present protease specificity profiling based on quantitative proteomics in combination with proteome-derived peptide libraries. Peptide libraries are generated by endoproteolytic digestion of proteomes without chemical modification of primary amines bef ... Full text Cite

Lysine-Specific Demethylase 1A (KDM1A/LSD1): Product Recognition and Kinetic Analysis of Full-Length Histones.

Journal Article Biochemistry · March 2016 Lysine-specific demethylase 1A (KDM1A/LSD1) is a FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively. Although the active site is expanded compared to that ... Full text Cite

The Chlamydia trachomatis Protease CPAF Contains a Cryptic PDZ-Like Domain with Similarity to Human Cell Polarity and Tight Junction PDZ-Containing Proteins.

Journal Article PLoS One · 2016 The need for more effective anti-chlamydial therapeutics has sparked research efforts geared toward further understanding chlamydial pathogenesis mechanisms. Recent studies have implicated the secreted chlamydial serine protease, chlamydial protease-like a ... Full text Link to item Cite

A rationally-designed chimeric KDM1A/KDM1B histone demethylase tower domain deletion mutant retaining enzymatic activity.

Journal Article FEBS letters · August 2015 A target with therapeutic potential, lysine-specific demethylase 1A (KDM1A) is a regulator of gene expression whose tower domain is a protein-protein interaction motif. This domain facilitates the interaction of KDM1A with coregulators and multiprotein com ... Full text Cite

KDM1 class flavin-dependent protein lysine demethylases.

Journal Article Biopolymers · July 2015 Flavin-dependent, lysine-specific protein demethylases (KDM1s) are a subfamily of amine oxidases that catalyze the selective posttranslational oxidative demethylation of methyllysine side chains within protein and peptide substrates. KDM1s participate in t ... Full text Cite

Reassessing the role of the secreted protease CPAF in Chlamydia trachomatis infection through genetic approaches.

Journal Article Pathog Dis · August 2014 The secreted Chlamydia protease CPAF cleaves a defined set of mammalian and Chlamydia proteins in vitro. As a result, this protease has been proposed to modulate a range of bacterial and host cellular functions. However, it has recently come into question ... Full text Link to item Cite

Sortases

Journal Article · August 29, 2013 Full text Cite

Sortase-catalyzed initiator attachment enables high yield growth of a stealth polymer from the C terminus of a protein.

Journal Article Macromolecular rapid communications · August 2013 Conventional methods for synthesizing protein/peptide-polymer conjugates, as a means to improve the pharmacological properties of therapeutic biomolecules, typically have drawbacks including low yield, non-trivial separation of conjugates from reactants, a ... 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

Lysine-specific histone demethylase 1 inhibitors control breast cancer proliferation in ERα-dependent and -independent manners.

Journal Article ACS Chem Biol · July 20, 2012 Lysine specific demethylase 1 (LSD1, also known as KDM1) is a histone modifying enzyme that regulates the expression of many genes important in cancer progression and proliferation. It is present in various transcriptional complexes including those contain ... Full text Link to item Cite

Proton-coupled electron transfer.

Journal Article Chemical reviews · July 2012 Full text Cite

Studies on the biosynthesis of the lipodepsipeptide antibiotic Ramoplanin A2.

Journal Article Bioorganic & medicinal chemistry · January 2012 Ramoplanin, a non-ribosomally synthesized peptide antibiotic, is highly effective against several drug-resistant Gram-positive bacteria, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), two i ... Full text Cite

Staphylococcus aureus sortase A contributes to the Trojan horse mechanism of immune defense evasion with its intrinsic resistance to Cys184 oxidation.

Journal Article Biochemistry · September 6, 2011 Staphylococcus aureus is a Gram-positive bacterial pathogen that causes serious infections which have become increasingly difficult to treat due to antimicrobial resistance and natural virulence strategies. Bacterial sortase enzymes are important virulence ... Full text Link to item Cite

Chlamydia protease-like activity factor (CPAF): characterization of proteolysis activity in vitro and development of a nanomolar affinity CPAF zymogen-derived inhibitor.

Journal Article Biochemistry · September 6, 2011 During infection of epithelial cells, the obligate intracellular pathogen Chlamydia trachomatis secretes the serine protease Chlamydia protease-like activity factor (CPAF) into the host cytosol to regulate a range of host cellular processes through targete ... Full text Link to item Cite

The Chlamydia protease CPAF regulates host and bacterial proteins to maintain pathogen vacuole integrity and promote virulence.

Journal Article Cell Host Microbe · July 21, 2011 The obligate intracellular bacterial pathogen Chlamydia trachomatis injects numerous effector proteins into the epithelial cell cytoplasm to manipulate host functions important for bacterial survival. In addition, the bacterium secretes a serine protease, ... Full text Link to item Cite

Found in translation: applications of protein and peptide molecular diversity.

Journal Article Current opinion in chemical biology · June 2011 Full text Cite

Thermodynamic characterization of the binding interaction between the histone demethylase LSD1/KDM1 and CoREST.

Journal Article Biochemistry · February 2011 Flavin-dependent histone demethylases catalyze the posttranslational oxidative demethylation of mono- and dimethylated lysine residues, producing formaldehyde and hydrogen peroxide in addition to the corresponding demethylated protein. In vivo, histone dem ... Full text Cite

Autocatalytic intramolecular isopeptide bond formation in gram-positive bacterial pili: a QM/MM simulation.

Journal Article Journal of the American Chemical Society · January 2011 Many gram-positive pathogens possess external pili or fimbriae with which they adhere to host cells during the infection process. Unusual dual intramolecular isopeptide bonds between Asn and Lys side chains within the N-terminal and C-terminal domains of t ... Full text Cite

Generation of ramoplanin-resistant Staphylococcus aureus.

Journal Article FEMS microbiology letters · September 2010 Ramoplanin is a lipoglycodepsipeptide antimicrobial active against clinically important Gram-positive bacteria including methicillin-resistant Staphylococcus aureus. To proactively examine ramoplanin resistance, we subjected S. aureus NCTC 8325-4 to serial ... Full text Cite

Sortase transpeptidases: insights into mechanism, substrate specificity, and inhibition.

Journal Article Biopolymers · January 2010 Gram-positive bacteria pose a serious healthcare threat. The growing antibiotic resistance epidemic creates a dire need for new antibiotic targets. The sortase family of enzymes is a promising target for antimicrobial therapy. This review covers the curren ... Full text Cite

A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential Lipid II docking interface.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · August 2009 The glycodepsipeptide antibiotic ramoplanin A2 is in late stage clinical development for the treatment of infections from Gram-positive pathogens, especially those that are resistant to first line antibiotics such as vancomycin. Ramoplanin A2 achieves its ... Full text Cite

Use of pH and kinetic isotope effects to establish chemistry as rate-limiting in oxidation of a peptide substrate by LSD1.

Journal Article Biochemistry · June 2009 The mechanism of oxidation of a peptide substrate by the flavoprotein lysine-specific demethylase (LSD1) has been examined using the effects of pH and isotopic substitution on steady-state and rapid-reaction kinetic parameters. The substrate contained the ... Full text Cite

Critical role of NOD2 in regulating the immune response to Staphylococcus aureus.

Journal Article Infect Immun · April 2009 NOD2 (the nucleotide-binding oligomerization domain containing protein 2) is known to be involved in host recognition of bacteria, although its role in the host response to Staphylococcus aureus infection is unknown. NOD2-deficient (Nod2(-/-)) mice and wil ... Full text Link to item Cite

Probing of the cis-5-phenyl proline scaffold as a platform for the synthesis of mechanism-based inhibitors of the Staphylococcus aureus sortase SrtA isoform.

Journal Article Bioorganic & medicinal chemistry · April 2009 cis-5-Phenyl prolinates with electrophilic substituents at the fourth position of a pyrrolidine ring were synthesized by 1,3-dipolar cycloaddition of arylimino esters with divinyl sulfone and acrylonitrile. 4-Vinylsulfonyl 5-phenyl prolinates inhibit Staph ... Full text Cite

Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism.

Journal Article The Journal of biological chemistry · March 2009 Sortases are a family of Gram-positive bacterial transpeptidases that anchor secreted proteins to bacterial cell surfaces. These include many proteins that play critical roles in the virulence of Gram-positive bacterial pathogens such that sortases are att ... Full text Cite

Facile synthesis of substituted trans-2-arylcyclopropylamine inhibitors of the human histone demethylase LSD1 and monoamine oxidases A and B.

Journal Article Bioorganic & medicinal chemistry letters · May 2008 A facile synthetic route to substituted trans-2-arylcyclopropylamines was developed to provide access to mechanism-based inhibitors of the human flavoenzyme oxidase lysine-specific histone demethylase LSD1 and related enzyme family members such as monoamin ... Full text Cite

Mutagenesis studies of substrate recognition and catalysis in the sortase A transpeptidase from Staphylococcus aureus.

Journal Article The Journal of biological chemistry · May 2008 The Staphylococcus aureus transpeptidase sortase A (SrtA) is responsible for anchoring a range of virulence- and colonization-associated proteins to the cell wall. SrtA recognizes substrates that contain a C-terminal LPXTG motif. This sequence is cleaved f ... Full text Cite

Mutational analysis of active site residues in the Staphylococcus aureus transpeptidase SrtA.

Journal Article Biochemistry · June 2007 In Staphylococcus aureus, virulence and colonization-associated surface proteins are covalently anchored to the cell wall by the transpeptidase Sortase A (SrtA). In order to better understand the contribution of specific active site residues to substrate r ... Full text Cite

trans-2-Phenylcyclopropylamine is a mechanism-based inactivator of the histone demethylase LSD1.

Journal Article Biochemistry · April 2007 The catalytic domain of the flavin-dependent human histone demethylase lysine-specific demethylase 1 (LSD1) belongs to the family of amine oxidases including polyamine oxidase and monoamine oxidase (MAO). We previously assessed monoamine oxidase inhibitors ... Full text Cite

Engineering the substrate specificity of Staphylococcus aureus Sortase A. The beta6/beta7 loop from SrtB confers NPQTN recognition to SrtA.

Journal Article The Journal of biological chemistry · March 2007 The Staphylococcus aureus transpeptidase Sortase A (SrtA) anchors virulence and colonization-associated surface proteins to the cell wall. SrtA selectively recognizes a C-terminal LPXTG motif, whereas the related transpeptidase Sortase B (SrtB) recognizes ... Full text Cite

Crossing a biological velvet rope.

Journal Article ACS chemical biology · July 2006 In contrast to our understanding of the composition of the outer membrane (OM) of Gram-negative bacteria, the biogenesis of this organelle has remained elusive. This is in part because factors involved in OM assembly have been refractive to chemical and bi ... Full text Cite

Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications.

Journal Article Chemistry & biology · June 2006 Demethylation of histone H3 lysine 4 is carried out by BHC110/LSD1, an enzyme with close homology to monoamine oxidases (MAO). Monoamine oxidase A or B are frequent targets of selective and nonselective small molecular inhibitors used for treatment of depr ... Full text Cite

Staphylococcus aureus sortase transpeptidase SrtA: insight into the kinetic mechanism and evidence for a reverse protonation catalytic mechanism.

Journal Article Biochemistry · August 2005 The Staphylococcus aureus transpeptidase SrtA catalyzes the covalent attachment of LPXTG-containing virulence and colonization-associated proteins to cell-wall peptidoglycan in Gram-positive bacteria. Recent structural characterizations of staphylococcal S ... Full text Cite

Facile syntheses of conformationally constrained analogues of lysine and homoglutamic acid

Journal Article Tetrahedron Letters · July 25, 2005 A facile divergent synthesis of the novel amino acid trans-4-aminoethyl-l- proline and trans-4-carboxymethyl-l-proline from commercially available trans-4-hydroxy-l-proline was developed. These conformationally constrained analogues of l-lysine and l-homog ... Full text Cite

A suppression strategy for antibiotic discovery.

Journal Article Chemistry & biology · October 2004 High-throughput phenotype screening and target identification have been combined in an effort to isolate antimicrobial, small-molecule therapeutics. This approach, developed by Brown and colleagues and reported in this issue, is a major technological advan ... Full text Cite

Inhibition of the Staphylococcus aureus sortase transpeptidase SrtA by phosphinic peptidomimetics.

Journal Article Bioorganic & medicinal chemistry · July 2004 During pathogenesis, Gram-positive bacteria utilize surface protein virulence factors such as the MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) to aid the initiation and propagation of infection through adherence to host end ... Full text Cite

Solvent dependence of intramolecular electron transfer in a helical oligoproline assembly.

Journal Article Journal of the American Chemical Society · April 2004 The helical oligoproline assembly CH3-CO-Pro-Pro-Pro-Pra(Ptzpn)-Pro-Pro-Pra(RuIIb2m2+ -Pro-Pro-Pra(Anq)-Pro-Pro-Pro-NH2, having a spatially ordered array of functional sites protruding from the proline backbone, has been prepared. The 13-residue assembly f ... Full text Cite

Profiling natural product biosynthesis.

Journal Article Chemistry & biology · March 2004 Natural products are a rich source of therapeutics; however, artificially reengineering the biosynthetic pathways that generate these compounds could potentially generate "designer" drugs. Last month in Chemistry & Biology, Burkart and coworkers reported t ... Full text Cite

Vinyl sulfones: inhibitors of SrtA, a transpeptidase required for cell wall protein anchoring and virulence in Staphylococcus aureus.

Journal Article Journal of the American Chemical Society · March 2004 Several small molecule vinyl sulfones were found to exhibit irreversible time-dependent inhibition of the Staphylococcus aureus sortase SrtA in vitro. A representative of these compounds was shown to impair the ability of S. aureus bacteria to bind fibrone ... Full text Cite

Development of a high-performance liquid chromatography assay and revision of kinetic parameters for the Staphylococcus aureus sortase transpeptidase SrtA.

Journal Article Analytical biochemistry · March 2004 The SrtA isoform of the Staphylococcus aureus sortase transpeptidase is responsible for the covalent attachment of virulence- and colonization-associated proteins to the bacterial peptidoglycan. Sortase utilizes two substrates, undecaprenol-pyrophosphoryl- ... Full text Cite

Analysis of the substrate specificity of the Staphylococcus aureus sortase transpeptidase SrtA.

Journal Article Biochemistry · February 2004 The Staphylococcus aureus sortase transpeptidase SrtA isoform is responsible for the covalent attachment of virulence and colonization-associated proteins to the bacterial peptidoglycan. SrtA utilizes two substrates, undecaprenol-pyrophosphoryl-MurNAc(GlcN ... Full text Cite

Techniques used to study transcription on chromatin templates.

Journal Article Methods in enzymology · January 2004 Full text Cite

Facile synthesis of site-specifically acetylated and methylated histone proteins: reagents for evaluation of the histone code hypothesis.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · October 2003 The functional capacity of genetically encoded histone proteins can be powerfully expanded by posttranslational modification. A growing body of biochemical and genetic evidence clearly links the unique combinatorial patterning of side chain acetylation, me ... Full text Cite

Phosphorus-based SAHA analogues as histone deacetylase inhibitors.

Journal Article Organic letters · August 2003 [structure: see text] Three analogues of suberoyl anilide hydroxamic acid (SAHA) with phosphorus metal-chelating functionalities were synthesized as inhibitors of histone deacetylases (HDACs). The compounds showed weak activity for HeLa nuclear extracts (I ... Full text Cite

Light-induced helix formation

Journal Article Journal of the American Chemical Society · October 30, 2002 This study shows that incorporation of [Rub2m-OH]2+ at the N-terminus of the Fs peptide enhances its stability by∼0.15 kcal/mol through the mechanism of dipole-dipole coupling at the excited state, suggesting that photoinduced charge generation at a well-c ... Full text Cite

An economical and preparative orthogonal solid phase synthesis of fluorescein and rhodamine derivatized peptides: FRET substrates for the Staphylococcus aureus sortase SrtA transpeptidase reaction.

Journal Article Chemical communications (Cambridge, England) · September 2002 An economical and preparative-scale orthogonal solid-phase method of incorporating carboxyrhodamine and carboxyfluorescein fluorescence resonance energy transfer (FRET) probes site-specifically into synthetic peptide substrates for the S. aureus Sortase tr ... Full text Cite

Functional analysis of the lipoglycodepsipeptide antibiotic ramoplanin.

Journal Article Chemistry & biology · August 2002 The peptide antibiotic ramoplanin is highly effective against several drug-resistant gram-positive bacteria, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), two important opportunistic human ... Full text Cite

Complexation of peptidoglycan intermediates by the lipoglycodepsipeptide antibiotic ramoplanin: minimal structural requirements for intermolecular complexation and fibril formation.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · May 2002 The peptide antibiotic ramoplanin inhibits bacterial peptidoglycan (PG) biosynthesis by interrupting late-stage membrane-associated glycosyltransferase reactions catalyzed by the transglycosylase and MurG enzymes. The mechanism of ramoplanin involves seque ... Full text Cite

Chemistry and biology of the ramoplanin family of peptide antibiotics.

Journal Article Biopolymers · January 2002 The peptide antibiotic ramoplanin factor A2 is a promising clinical candidate for treatment of Gram-positive bacterial infections that are resistant to antibiotics such as glycopeptides, macrolides, and penicillins. Since its discovery in 1984, no clinical ... Full text Cite

An economical and preparative orthogonal solid phase synthesis of fluorescein and rhodamine derivatized peptides: FRET substrates for the Staphylococcus aureus sortase SrtA transpeptidase reaction

Journal Article Chemical Communications · 2002 An economical and preparative-scale orthogonal solid-phase method of incorporating carboxyrhodamine and carboxy-fluorescein fluorescence resonance energy transfer (FRET) probes site-specifically into synthetic peptide substrates for the S. aureus Sortase t ... Cite

Synthesis of P(1)-Citronellyl-P(2)-alpha-D-pyranosyl pyrophosphates as potential substrates for the E. coli undecaprenyl-pyrophosphoryl-N-acetylglucoseaminyl transferase MurG.

Journal Article Bioorganic & medicinal chemistry letters · December 2001 P(1)-Citronellyl-P(2)-alpha-D-pyranosyl pyrophosphates containing alpha-D-N-acetylglucoseaminyl, alpha-D-glucosyl, and alpha-D-N-acetylmuramyl carbohydrates were synthesized and used in substrate specificity studies of the Escherichia coli MurG enzyme. Oxa ... Full text Cite

4'-Aminomethyl-2,2'-bipyridyl-4-carboxylic acid (Abc) and related derivatives: Novel bipyridine amino acids for the solid-phase incorporation of a metal coordination site within a peptide backbone

Journal Article Tetrahedron · June 30, 2000 The novel bipyridyl amino acid, 4'-aminomethyl-2,2'-bipyridyl-4- carboxylic acid (Abc), and related Boc- and Fmoc-protected derivatives were synthesized to provide high-affinity bidentate metal-binding amino acid modules for the solid-phase peptide synthes ... Full text Cite

Synergy and duality in peptide antibiotic mechanisms.

Journal Article Current opinion in chemical biology · December 1999 The molecular mechanisms by which peptide antibiotics disrupt bacterial DNA synthesis, protein biosynthesis, cell wall biosynthesis, and membrane integrity are diverse, yet historically have been understood to follow a theme of one antibiotic, one inhibito ... Full text Cite

Homologs of the vancomycin resistance D-Ala-D-Ala dipeptidase VanX in Streptomyces toyocaensis, Escherichia coli and Synechocystis: attributes of catalytic efficiency, stereoselectivity and regulation with implications for function.

Journal Article Chemistry & biology · September 1998 BackgroundVancomycin-resistant enterococci are pathogenic bacteria that have altered cell-wall peptidoglycan termini (D-alanyl-D-lactate [D-Ala-D-lactate] instead of D-alanyl-D-alanine [D-Ala-D-Ala]), which results in a 1000-fold decreased affinit ... Full text Cite

Mutational analysis of potential zinc-binding residues in the active site of the enterococcal D-Ala-D-Ala dipeptidase VanX.

Journal Article Biochemistry · August 1997 VanX, one of the five proteins required for the vancomycin-resistant phenotype in clinically pathogenic Enterococci, is a zinc-containing d-Ala-d-Ala dipeptidase. To identify potential zinc ligands and begin defining the active site residues, we have mutat ... Full text Cite

Photochemical energy conversion in a helical oligoproline assembly.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · August 1996 A general method is described for constructing a helical oligoproline assembly having a spatially ordered array of functional sites protruding from a proline-II helix. Three different redox-active carboxylic acids were coupled to the side chain of cis-4-am ... Full text Cite

Synthesis of redox derivatives of lysine and their use in solid-phase synthesis of a light-harvesting peptide

Journal Article Tetrahedron · January 23, 1995 Redox-active amino acids were synthesized for incorporation into peptide assemblies to study photoinitiated electron or energy transfer. 4′-Methyl-2,2′-bipyridine-4-carboxylic acid was obtained in 72% yield by consecutive SeO2 and Ag2O oxidation without is ... Full text Cite

Engineering of a 129-residue tripod protein by chemoselective ligation of proline-II helices

Journal Article Tetrahedron · January 1, 1995 A 129-residue tripod protein was designed, synthesized, and biophysically characterized. This receptor-adhesive modular protein contained three 30-residue proline-II helices linked to a 9-residue proline-II helix through thioether bonds. Coupling of 6-male ... Full text Cite

Spectroscopic Study of Electron Transfer in a Trifunctional Lysine with Anthraquinone as the Electron Acceptor

Journal Article Inorganic Chemistry · June 1, 1994 The transient properties of the redox-active amino acid dyads [Anq-Lys(RuIIb2m)2+-OCH3](PF6)2 and [Boc-Lys(RuIIb2m)2+-NH-prPTZ](PF6)2 and the trifunctionalized amino acid [Anq-Lys(RuIIb2m)2+-NH-prPTZ](PF6)2, where Anq is 9,10-anthraquinone-2-carbonyl, Lys ... Full text Cite

Photoinduced Electron Transfer in Amino Acid Assemblies

Journal Article Journal of the American Chemical Society · June 1, 1993 The preparation and photophysical characterization of a series of redox-active lysines and related model compounds based on polypyridyl ruthenium complexes are described. Donor-chromophore-acceptor triad 1, [PTZpn-Lys(RuIIb2m)2+-NH-prPQ2+] (PF6−)4 (see bel ... Full text Cite