Scholars@Duke
Jiyong Hong

Jiyong Hong

Professor of Chemistry
Chemistry
jiyong.hong@duke.edu
Box 90346, Durham, NC 27708-0347
3220 French Science Center, 124 Science Drive, Durham, NC 27708
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Selected Publications

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22-modified FK520 analog against C. neoformans.

Journal Article mBio · October 31, 2023 Fungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited, and the development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human ... Full text Link to item Cite

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22 modified FK520 analog against C. neoformans.

Journal Article bioRxiv · July 11, 2023 UNLABELLED: Fungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections by Cryptococcus neoformans are associated with high mortality, emphasizing the ... Full text Link to item Cite

Development of LpxH Inhibitors Chelating the Active Site Dimanganese Metal Cluster of LpxH.

Journal Article ChemMedChem · June 1, 2023 Despite the widespread emergence of multidrug-resistant nosocomial Gram-negative bacterial infections and the major public health threat it brings, no new class of antibiotics for Gram-negative pathogens has been approved over the past five decades. Theref ... Full text Link to item Cite

Manassantin A inhibits tumour growth under hypoxia through the activation of chaperone-mediated autophagy by modulating Hsp90 activity.

Journal Article Br J Cancer · April 2023 BACKGROUND: Chaperon-mediated autophagy (CMA) has taken on a new emphasis in cancer biology. However, the roles of CMA in hypoxic tumours are poorly understood. We investigated the anti-tumour effects of the natural product ManA through the activation of C ... Full text Link to item Cite

Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy.

Journal Article NAR Cancer · March 2023 DNA damage tolerance and mutagenesis are hallmarks and enabling characteristics of neoplastic cells that drive tumorigenesis and allow cancer cells to resist therapy. The 'Y-family' trans-lesion synthesis (TLS) DNA polymerases enable cells to replicate dam ... Full text Open Access Link to item Cite

Corrigendum: Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition.

Journal Article Front Med (Lausanne) · 2023 [This corrects the article DOI: 10.3389/fmed.2022.999004.]. ... Full text Link to item Cite

Methotrexate recognition by the human reduced folate carrier SLC19A1.

Journal Article Nature · September 2022 Folates are essential nutrients with important roles as cofactors in one-carbon transfer reactions, being heavily utilized in the synthesis of nucleic acids and the metabolism of amino acids during cell division1,2. Mammals lack de novo folate synthesis pa ... Full text Link to item Cite

Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity Exhibit In Vivo Therapeutic Efficacy against Cryptococcus.

Journal Article mBio · June 28, 2022 Calcineurin is an essential virulence factor that is conserved across human fungal pathogens, including Cryptococcus neoformans, Aspergillus fumigatus, and Candida albicans. Although an excellent target for antifungal drug development, the serine-threonine ... Full text Open Access Link to item Cite

SARS-CoV-2 hijacks host cell genome instability pathways.

Journal Article Res Sq · April 14, 2022 The repertoire of coronavirus disease 2019 (COVID-19)-mediated adverse health outcomes has continued to expand in infected patients, including the susceptibility to developing long-COVID; however, the molecular underpinnings at the cellular level are poorl ... Full text Link to item Cite

Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition.

Journal Article Front Med (Lausanne) · 2022 Colorectal cancer (CRC) is the third most prevalent form of cancer in the United States and results in over 50,000 deaths per year. Treatments for metastatic CRC are limited, and therefore there is an unmet clinical need for more effective therapies. In ou ... Full text Link to item Cite

REV1 Inhibition Enhances Radioresistance and Autophagy.

Journal Article Cancers (Basel) · October 21, 2021 Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations sug ... Full text Link to item Cite

REV1 Inhibition Enhances Radioresistance and Autophagy

Journal Article · September 13, 2021 Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observat ... Full text Cite

Synthetic efforts toward the bicyclo[3.2.1]octane fragment of rhodojaponin III.

Journal Article Tetrahedron letters · May 2021 Rhodojaponin III is a grayanane-type diterpenoid natural product with a novel chemical scaffold. It shows potent antinociceptive activity and may represent a new class of natural non-opioid analgesics with a novel mode of action. We explored the Au(I)-cata ... Full text Cite

Structure- and Ligand-Dynamics-Based Design of Novel Antibiotics Targeting Lipid A Enzymes LpxC and LpxH in Gram-Negative Bacteria.

Journal Article Acc Chem Res · April 6, 2021 Bacterial infections caused by multi-drug-resistant Gram-negative pathogens pose a serious threat to public health. Gram-negative bacteria are characterized by the enrichment of lipid A-anchored lipopolysaccharide (LPS) or lipooligosaccharide (LOS) in the ... Full text Link to item Cite

Synthesis and evaluation of cyclopentane-based muraymycin analogs targeting MraY.

Journal Article Eur J Med Chem · April 5, 2021 Antibiotic resistance is one of the most challenging global health issues and presents an urgent need for the development of new antibiotics. In this regard, phospho-MurNAc-pentapeptide translocase (MraY), an essential enzyme in the early stages of peptido ... Full text Link to item Cite

REV1 inhibitor JH-RE-06 enhances tumor cell response to chemotherapy by triggering senescence hallmarks.

Journal Article Proc Natl Acad Sci U S A · November 17, 2020 REV1/POLζ-dependent mutagenic translesion synthesis (TLS) promotes cell survival after DNA damage but is responsible for most of the resulting mutations. A novel inhibitor of this pathway, JH-RE-06, promotes cisplatin efficacy in cancer cells and mouse xen ... Full text Link to item Cite

Synthesis and evaluation of sulfonyl piperazine LpxH inhibitors.

Journal Article Bioorg Chem · September 2020 Featured Publication The UDP-2,3-diacylglucosamine pyrophosphate hydrolase LpxH is essential in lipid A biosynthesis and has emerged as a promising target for the development of novel antibiotics against multidrug-resistant Gram-negative pathogens. Recently, we reported the cr ... Full text Link to item Cite

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22-modified FK520 analog against C. neoformans.

Journal Article mBio · October 31, 2023 Fungal infections cause significant morbidity and mortality globally. The therapeutic armamentarium against these infections is limited, and the development of antifungal drugs has been hindered by the evolutionary conservation between fungi and the human ... Full text Link to item Cite

Enhanced fungal specificity and in vivo therapeutic efficacy of a C-22 modified FK520 analog against C. neoformans.

Journal Article bioRxiv · July 11, 2023 UNLABELLED: Fungal infections are of mounting global concern, and the current limited treatment arsenal poses challenges when treating such infections. In particular, infections by Cryptococcus neoformans are associated with high mortality, emphasizing the ... Full text Link to item Cite

Development of LpxH Inhibitors Chelating the Active Site Dimanganese Metal Cluster of LpxH.

Journal Article ChemMedChem · June 1, 2023 Despite the widespread emergence of multidrug-resistant nosocomial Gram-negative bacterial infections and the major public health threat it brings, no new class of antibiotics for Gram-negative pathogens has been approved over the past five decades. Theref ... Full text Link to item Cite

Manassantin A inhibits tumour growth under hypoxia through the activation of chaperone-mediated autophagy by modulating Hsp90 activity.

Journal Article Br J Cancer · April 2023 BACKGROUND: Chaperon-mediated autophagy (CMA) has taken on a new emphasis in cancer biology. However, the roles of CMA in hypoxic tumours are poorly understood. We investigated the anti-tumour effects of the natural product ManA through the activation of C ... Full text Link to item Cite

Roles of trans-lesion synthesis (TLS) DNA polymerases in tumorigenesis and cancer therapy.

Journal Article NAR Cancer · March 2023 DNA damage tolerance and mutagenesis are hallmarks and enabling characteristics of neoplastic cells that drive tumorigenesis and allow cancer cells to resist therapy. The 'Y-family' trans-lesion synthesis (TLS) DNA polymerases enable cells to replicate dam ... Full text Open Access Link to item Cite

Corrigendum: Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition.

Journal Article Front Med (Lausanne) · 2023 [This corrects the article DOI: 10.3389/fmed.2022.999004.]. ... Full text Link to item Cite

Methotrexate recognition by the human reduced folate carrier SLC19A1.

Journal Article Nature · September 2022 Folates are essential nutrients with important roles as cofactors in one-carbon transfer reactions, being heavily utilized in the synthesis of nucleic acids and the metabolism of amino acids during cell division1,2. Mammals lack de novo folate synthesis pa ... Full text Link to item Cite

Structure-Guided Synthesis of FK506 and FK520 Analogs with Increased Selectivity Exhibit In Vivo Therapeutic Efficacy against Cryptococcus.

Journal Article mBio · June 28, 2022 Calcineurin is an essential virulence factor that is conserved across human fungal pathogens, including Cryptococcus neoformans, Aspergillus fumigatus, and Candida albicans. Although an excellent target for antifungal drug development, the serine-threonine ... Full text Open Access Link to item Cite

SARS-CoV-2 hijacks host cell genome instability pathways.

Journal Article Res Sq · April 14, 2022 The repertoire of coronavirus disease 2019 (COVID-19)-mediated adverse health outcomes has continued to expand in infected patients, including the susceptibility to developing long-COVID; however, the molecular underpinnings at the cellular level are poorl ... Full text Link to item Cite

Psymberin, a marine-derived natural product, induces cancer cell growth arrest and protein translation inhibition.

Journal Article Front Med (Lausanne) · 2022 Colorectal cancer (CRC) is the third most prevalent form of cancer in the United States and results in over 50,000 deaths per year. Treatments for metastatic CRC are limited, and therefore there is an unmet clinical need for more effective therapies. In ou ... Full text Link to item Cite

REV1 Inhibition Enhances Radioresistance and Autophagy.

Journal Article Cancers (Basel) · October 21, 2021 Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations sug ... Full text Link to item Cite

REV1 Inhibition Enhances Radioresistance and Autophagy

Journal Article · September 13, 2021 Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observat ... Full text Cite

Synthetic efforts toward the bicyclo[3.2.1]octane fragment of rhodojaponin III.

Journal Article Tetrahedron letters · May 2021 Rhodojaponin III is a grayanane-type diterpenoid natural product with a novel chemical scaffold. It shows potent antinociceptive activity and may represent a new class of natural non-opioid analgesics with a novel mode of action. We explored the Au(I)-cata ... Full text Cite

Structure- and Ligand-Dynamics-Based Design of Novel Antibiotics Targeting Lipid A Enzymes LpxC and LpxH in Gram-Negative Bacteria.

Journal Article Acc Chem Res · April 6, 2021 Bacterial infections caused by multi-drug-resistant Gram-negative pathogens pose a serious threat to public health. Gram-negative bacteria are characterized by the enrichment of lipid A-anchored lipopolysaccharide (LPS) or lipooligosaccharide (LOS) in the ... Full text Link to item Cite

Synthesis and evaluation of cyclopentane-based muraymycin analogs targeting MraY.

Journal Article Eur J Med Chem · April 5, 2021 Antibiotic resistance is one of the most challenging global health issues and presents an urgent need for the development of new antibiotics. In this regard, phospho-MurNAc-pentapeptide translocase (MraY), an essential enzyme in the early stages of peptido ... Full text Link to item Cite

REV1 inhibitor JH-RE-06 enhances tumor cell response to chemotherapy by triggering senescence hallmarks.

Journal Article Proc Natl Acad Sci U S A · November 17, 2020 REV1/POLζ-dependent mutagenic translesion synthesis (TLS) promotes cell survival after DNA damage but is responsible for most of the resulting mutations. A novel inhibitor of this pathway, JH-RE-06, promotes cisplatin efficacy in cancer cells and mouse xen ... Full text Link to item Cite

Synthesis and evaluation of sulfonyl piperazine LpxH inhibitors.

Journal Article Bioorg Chem · September 2020 Featured Publication The UDP-2,3-diacylglucosamine pyrophosphate hydrolase LpxH is essential in lipid A biosynthesis and has emerged as a promising target for the development of novel antibiotics against multidrug-resistant Gram-negative pathogens. Recently, we reported the cr ... Full text Link to item Cite

Evaluation of Manassantin A Tetrahydrofuran Core Region Analogues and Cooperative Therapeutic Effects with EGFR Inhibition.

Journal Article Journal of medicinal chemistry · July 2020 Featured Publication Tumors adapt to hypoxia by regulating angiogenesis, metastatic potential, and metabolism. These adaptations mediated by hypoxia-inducible factor 1 (HIF-1) make tumors more aggressive and resistant to chemotherapy and radiation. Therefore, HIF-1 is a valida ... Full text Cite

Resveratrol Protects Against Hydroquinone-Induced Oxidative Threat in Retinal Pigment Epithelial Cells.

Journal Article Invest Ophthalmol Vis Sci · April 9, 2020 Featured Publication PURPOSE: Oxidative stress in retinal pigment epithelial (RPE) cells is associated with age-related macular degeneration (AMD). Resveratrol exerts a range of protective biologic effects, but its mechanism(s) are not well understood. The aim of this study wa ... Full text Open Access Link to item Cite

Structural basis of the UDP-diacylglucosamine pyrophosphohydrolase LpxH inhibition by sulfonyl piperazine antibiotics.

Journal Article Proc Natl Acad Sci U S A · February 25, 2020 The UDP-2,3-diacylglucosamine pyrophosphate hydrolase LpxH is an essential lipid A biosynthetic enzyme that is conserved in the majority of gram-negative bacteria. It has emerged as an attractive novel antibiotic target due to the recent discovery of an Lp ... Full text Link to item Cite

A Stereoselective Formal Synthesis of Quinolizidine (–)-217A

Journal Article European Journal of Organic Chemistry · February 14, 2020 The stereoselective formal synthesis of quinolizidine alkaloid (–)-217A was achieved by utilizing a combination of the dithiane coupling reaction and the organocatalytic aza-conjugate addition reaction promoted by the gem-disubstituent effect to provide th ... Full text Cite

Length Specificity and Polymerization Mechanism of (1,3)-β-d-Glucan Synthase in Fungal Cell Wall Biosynthesis.

Journal Article Biochemistry · February 11, 2020 (1,3)-β-d-Glucan synthase (GS) catalyzes formation of the linear (1,3)-β-d-glucan in the fungal cell wall and is a target of clinically approved antifungal antibiotics. The catalytic subunit of GS, FKS protein, does not exhibit significant sequence homolog ... Full text Link to item Cite

Synthesis and Biological Evaluation of Subglutinol Analogs for Immunomodulatory Agents.

Journal Article J Med Chem · January 9, 2020 Autoimmune diseases are chronic inflammatory diseases associated with high morbidity and mortality. Treatment options for autoimmune diseases have increased over the past several decades, but they are, in general, limited in their clinical efficacy due to ... Full text Link to item Cite

Chemical logic of MraY inhibition by antibacterial nucleoside natural products.

Journal Article Nat Commun · July 2, 2019 Novel antibacterial agents are needed to address the emergence of global antibiotic resistance. MraY is a promising candidate for antibiotic development because it is the target of five classes of naturally occurring nucleoside inhibitors with potent antib ... Full text Link to item Cite

A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy.

Journal Article Cell · June 27, 2019 Intrinsic and acquired drug resistance and induction of secondary malignancies limit successful chemotherapy. Because mutagenic translesion synthesis (TLS) contributes to chemoresistance as well as treatment-induced mutations, targeting TLS is an attractiv ... Full text Link to item Cite

Synthesis and Analysis of Natural-Product-Like Macrocycles by Tandem Oxidation/Oxa-Conjugate Addition Reactions.

Journal Article Chemistry (Weinheim an der Bergstrasse, Germany) · May 2019 As traditional small-molecule drug discovery programs focus on a relatively narrow range of chemical space, most human proteins are viewed as unreachable targets. Consequently, there is a strong interest in expanding the chemical space in drug discovery be ... Full text Cite

Structure-Activity Relationship of Sulfonyl Piperazine LpxH Inhibitors Analyzed by an LpxE-Coupled Malachite Green Assay.

Journal Article ACS Infect Dis · April 12, 2019 The UDP-2,3-diacylglucosamine pyrophosphatase LpxH in the Raetz pathway of lipid A biosynthesis is an essential enzyme in the vast majority of Gram-negative pathogens and an excellent novel antibiotic target. The 32P-radioautographic thin-layer chromatogra ... Full text Link to item Cite

In silico Screening and Evaluation of Plasmodium falciparum Protein Kinase 5 (PK5) Inhibitors.

Journal Article ChemMedChem · December 2018 An in silico screen of 350 000 commercially available compounds was conducted with an unbiased approach to identify potential malaria inhibitors that bind to the Plasmodium falciparum protein kinase 5 (PfPK5) ATP-binding site. PfPK5 is a cyclin-dependent k ... Full text Cite

Synthetic efforts towards the stereoselective synthesis of NF00659B1.

Journal Article Bioorganic & medicinal chemistry letters · September 2018 NF00659B1 is a novel α-pyrone diterpenoid natural product with potent anti-colon cancer activity. A stereoselective approach to the 2,2-dimethyl oxepanol core of NF00659B1 is described enlisting a sequence of olefinic ester ring-closi ... Full text Cite

Design and synthesis of a natural product-like macrocycle library containing tetrahydropyran moieties

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 19, 2018 Link to item Cite

Synthesis and biological evaluation of largazole zinc-binding group analogs.

Journal Article Bioorganic & medicinal chemistry · June 2017 Histone acetylation is an extensively investigated post-translational modification that plays an important role as an epigenetic regulator. It is controlled by histone acetyl transferases (HATs) and histone deacetylases (HDACs). The overexpression of HDACs ... Full text Cite

Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma.

Journal Article JCI insight · June 2017 Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or gen ... Full text Cite

Formal Synthesis of (+)-Laurencin by Gold(I)-Catalyzed Intramolecular Dehydrative Alkoxylation.

Journal Article Chemistry (Weinheim an der Bergstrasse, Germany) · May 2017 8-Membered cyclic ethers are found in a wide range of natural products; however, they are challenging synthetic targets due to enthalpic and entropic barriers. The gold(I)-catalyzed intramolecular dehydrative alkoxylation of ω-hydroxy allylic alcohols was ... Full text Cite

Exploration of gold(I)-catalyzed alkoxylation for formal synthesis of (+)-laurencin

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · April 2, 2017 Link to item Cite

Synthesis and biological evaluation of sulfonyl piperazine derivatives for LpxH inhibition

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · April 2, 2017 Link to item Cite

Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes.

Journal Article J Immunol Methods · November 2016 T and B lymphocytes undergo metabolic re-programming upon activation that is essential to allow bioenergetics, cell survival, and intermediates for cell proliferation and function. To support changes in the activity of signaling pathways and to provide suf ... Full text Link to item Cite

Advances in the synthesis of glycosidic macrolides: clavosolides A-D and cyanolide A.

Journal Article Natural product reports · November 2016 Covering: 2005 to 2016Clavosolides A-D and cyanolide A are glycosidic macrolides and represent a new family of marine natural products. They possess a number of unusual structural features and have attracted considerable interest from the synthetic communi ... Full text Cite

Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements.

Journal Article J Proteome Res · August 5, 2016 Manassantin A is a natural product that has been shown to have anticancer activity in cell-based assays, but has a largely unknown mode-of-action. Described here is the use of two different energetics-based approaches to identify protein targets of manassa ... Full text Link to item Cite

Structural insights into inhibition of lipid I production in bacterial cell wall synthesis.

Journal Article Nature · May 26, 2016 Antibiotic-resistant bacterial infection is a serious threat to public health. Peptidoglycan biosynthesis is a well-established target for antibiotic development. MraY (phospho-MurNAc-pentapeptide translocase) catalyses the first and an essential membrane ... Full text Link to item Cite

Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition.

Journal Article J Med Chem · October 8, 2015 To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and res ... Full text Link to item Cite

Total Synthesis of Clavosolide A via Tandem Allylic Oxidation/Oxa-Conjugate Addition Reaction.

Journal Article Tetrahedron letters · June 2015 The tandem allylic oxidation/oxa-conjugate addition reaction promoted by the gem-disubstituent effect in conjunction with the NHC-mediated oxidative esterification was explored for the facile synthesis of clavosolide A. ... Full text Cite

Subglutinol A, an immunosuppressive α-pyrone diterpenoid from Fusarium subglutinans, acts as an estrogen receptor antagonist.

Journal Article Biochemical and biophysical research communications · June 2015 Subglutinol A is an immunosuppressive α-pyrone diterpenoid isolated from Fusarium subglutinans that exhibits osteogenic activity. Several non-steroid mycotoxins isolated from various strains of Fusarium fungi exhibit female steroid hormone activities. In t ... Full text Cite

Design, synthesis, and biological evaluation of manassantin analogues for HIF-1 alpha inhibition

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · March 22, 2015 Link to item Cite

An overview of naturally occurring histone deacetylase inhibitors.

Journal Article Current topics in medicinal chemistry · January 2015 Histone deacetylases (HDACs) have recently emerged as key elements in epigenetic control of gene expression. Due to the implication of HDACs in a variety of diseases ranging from cancer to neurodegenerative disorder, HDAC inhibitors have received increased ... Full text Cite

Natural product synthesis at the interface of chemistry and biology.

Journal Article Chemistry (Weinheim an der Bergstrasse, Germany) · August 2014 Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhle ... Full text Cite

Evaluation of class I HDAC isoform selectivity of largazole analogues.

Journal Article Bioorganic & medicinal chemistry letters · August 2014 Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The majority of largazole analogues to date have modified the thiazole-thiazoline and the warhead moiety. In order to elucidate class I-specific structure-activity relationships, ... Full text Cite

Modulation of Activity Profiles for Largazole-Based HDAC Inhibitors through Alteration of Prodrug Properties.

Journal Article ACS medicinal chemistry letters · August 2014 Largazole is a potent and class I-selective histone deacetylase (HDAC) inhibitor purified from marine cyanobacteria and was demonstrated to possess antitumor activity. Largazole employs a unique prodrug strategy, via a thioester moiety, to liberate the bio ... Full text Cite

Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters.

Journal Article Elife · July 31, 2014 Concentrative nucleoside transporters (CNTs) are responsible for cellular entry of nucleosides, which serve as precursors to nucleic acids and act as signaling molecules. CNTs also play a crucial role in the uptake of nucleoside-derived drugs, including an ... Full text Link to item Cite

Biological evaluation of subglutinol a as a novel immunosuppressive agent for inflammation intervention.

Journal Article ACS Med Chem Lett · May 8, 2014 Subglutinol A (1) is an immunosuppressive natural product isolated from Fusarium subglutinans, an endophytic fungus from the vine Tripterygium wilfordii. We show that 1 exerts multimodal immune-suppressive effects on activated T cells in vitro: subglutinol ... Full text Link to item Cite

Synthesis of α,α'-trans-oxepanes through an organocatalytic oxa-conjugate addition reaction.

Journal Article Organic letters · May 2014 Oxepanes are found in a wide range of natural products; however, they are challenging synthetic targets due to enthalpic and entropic barriers. Organocatalytic oxa-conjugate addition reactions promoted by the gem-disubstituent (Thorpe-Ingold) effect stereo ... Full text Cite

Largazole pharmacokinetics in rats by LC-MS/MS.

Journal Article Marine drugs · March 2014 A highly sensitive and specific LC-MS/MS method for the quantitation of largazole thiol, the active species of the marine-derived preclinical histone deacetylase inhibitor, largazole (prodrug), was developed and validated. Largazole thiol was extracted wit ... Full text Cite

False-positive rate determination of protein target discovery using a covalent modification- and mass spectrometry-based proteomics platform.

Journal Article Journal of the American Society for Mass Spectrometry · January 2014 Detection and quantitation of protein-ligand binding interactions is important in many areas of biological research. Stability of proteins from rates of oxidation (SPROX) is an energetics-based technique for identifying the proteins targets of ligands in c ... Full text Cite

Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis.

Journal Article Science · August 30, 2013 MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl ph ... Full text Link to item Cite

Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms.

Journal Article Oncogene · March 2013 Aggressive cancers often express E-cadherin in cytoplasmic vesicles rather than on the plasma membrane and this may contribute to the invasive phenotype of these tumors. Therapeutic strategies are not currently available that restore the anti-invasive func ... Full text Cite

Crystal structure of MraY, an essential membrane enzyme for bacterial cell wall synthesis

Journal Article Science · 2013 MraY (phospho-MurNAc-pentapeptide translocase) is an integral membrane enzyme that catalyzes an essential step of bacterial cell wall biosynthesis: the transfer of the peptidoglycan precursor phospho-MurNAc-pentapeptide to the lipid carrier undecaprenyl ph ... Full text Cite

Manipulating JNK signaling with (--)-zuonin A.

Journal Article ACS chemical biology · November 2012 Recently, in a virtual screening strategy to identify new compounds targeting the D-recruitment site (DRS) of the c-Jun N-terminal kinases (JNKs), we identified the natural product (-)-zuonin A. Here we report the asymmetric synthesis of (-)-zuonin A and i ... Full text Cite

From in Silico Discovery to intra-Cellular Activity: Targeting JNK-Protein Interactions with Small Molecules.

Journal Article ACS medicinal chemistry letters · August 2012 The JNK-JIP1 interaction represents an attractive target for the selective inhibition of JNK-mediated signaling. We report a virtual screening (VS) workflow, based on a combination of three-dimensional shape and electrostatic similarity to discover novel s ... Full text Cite

N-Heterocyclic carbene catalyzed oxidative macrolactonization: total synthesis of (+)-dactylolide.

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

Largazole: from discovery to broad-spectrum therapy.

Journal Article Natural product reports · April 2012 The cyclic depsipeptide largazole from a cyanobacterium of the genus Symploca is a marine natural product with a novel chemical scaffold and potently inhibits class I histone deacetylases (HDACs). Largazole possesses highly differential growth-inhibitory a ... Full text Cite

Immunosuppressive effects of subglutinol derivatives.

Journal Article ChemMedChem · February 2012 Full text Cite

Preface

Book · December 1, 2011 Cite

Stereoselective synthesis of 2,6-trans-tetrahydropyran via primary diamine-catalyzed oxa-conjugate addition reaction of α,β-unsaturated ketone: total synthesis of psymberin.

Journal Article Organic letters · November 2011 The total synthesis of psymberin was achieved employing a readily available chiral epoxide to prepare two of the three subunits in the natural product. The key reaction was a highly stereoselective organocatalytic oxa-conjugate addition reaction of α,β-uns ... Full text Cite

Stereoselective formal synthesis of leucascandrolide A

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

A formal synthesis of SCH 351448.

Journal Article Organic letters · July 2011 An efficient formal synthesis of SCH 351448 was accomplished through the tandem cross-metathesis (CM)/oxa-Michael, the 1,4-syn aldol, the tandem oxidation/oxa-Michael, and the Suzuki coupling reaction. ... Full text Cite

Role of natural product diversity in chemical biology.

Journal Article Current opinion in chemical biology · June 2011 Through the natural selection process, natural products possess a unique and vast chemical diversity and have been evolved for optimal interactions with biological macromolecules. Owing to their diversity, target affinity, and specificity, natural products ... Full text Cite

A stereoselective formal synthesis of leucascandrolide A.

Journal Article Organic letters · May 2011 A stereoselective formal synthesis of leucascandrolide A was accomplished through the tandem and organocatalytic oxa-Michael reactions, which were promoted by the gem-disubstituent effect, in conjunction with the dithiane coupling reaction. ... Full text Cite

Characterization of Fe(III) sequestration by an analog of the cytotoxic siderophore brasilibactin A: implications for the iron transport mechanism in mycobacteria.

Journal Article Metallomics : integrated biometal science · May 2011 Mycobacteria such as M. tuberculosis represent a significant health concern throughout much of the developing world. In mycobacteria and other pathogenic bacteria, an important virulence factor is the ability of the bacterium to obtain iron from its host. ... Full text Cite

Stereoselective synthesis of 2,6-cis- and 2,6-trans-piperidines through organocatalytic aza-Michael reactions: a facile synthesis of (+)-myrtine and (-)-epimyrtine.

Journal Article Organic letters · February 2011 Both 2,6-cis- and 2,6-trans-piperidines were prepared from common substrates through organocatalytic aza-Michael reactions promoted by the gem-disubstituent effect in conjunction with dithiane coupling reactions. The organocatalytic aza-Michael reaction en ... Full text Cite

In Vitro and In Vivo Osteogenic Activity of Largazole

Journal Article ACS Med. Chem. Lett. · 2011 Cite

Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor.

Journal Article The Journal of pharmacology and experimental therapeutics · November 2010 Histone deacetylases (HDACs) are validated targets for anticancer therapy as attested by the approval of suberoylanilide hydroxamic acid (SAHA) and romidepsin (FK228) for treating cutaneous T cell lymphoma. We recently described the bioassay-guided isolati ... Full text Cite

Total synthesis, assignment of the absolute stereochemistry, and structure-activity relationship studies of subglutinols A and B.

Journal Article Chemistry, an Asian journal · August 2010 Immunosuppressive drugs are used to prevent rejection of transplanted organs and treat autoimmune diseases. Clinically approved immunosuppressive drugs possess undesirable side effects, including acute neurological toxicity, chronic nephrotoxicity, and ost ... Full text Cite

Total synthesis of cyanolide A and confirmation of its absolute configuration.

Journal Article Organic letters · June 2010 The tandem allylic oxidation/oxa-Michael reaction promoted by the gem-disubstituent effect and the 2-methyl-6-nitrobenzoic anhydride (MNBA)-mediated dimerization were explored for the efficient and facile synthesis of cyanolide A. ... Full text Open Access Cite

A facile and efficient synthesis of 4-hydroxy-2,6-cis-tetrahydropyrans via tandem cross-metathesis/thermal S(N)2' reaction: protecting-group-free synthesis of (+/-)-diospongin A.

Journal Article Organic letters · November 2009 The tandem cross-metathesis/thermal S(N)2' reaction was explored for the facile and efficient synthesis of 4-hydroxy-2,6-cis-tetrahydropyrans. The mildness of the thermal conditions allowed for the synthesis of 4-hydroxy-2,6-cis-tetrahydropyrans from base- ... Full text Cite

Identification of 3-hydroxy-2-(3-hydroxyphenyl)-4H-1-benzopyran-4-ones as isoform-selective PKC-zeta inhibitors and potential therapeutics for psychostimulant abuse.

Journal Article Mol Biosyst · September 2009 From a screen of small molecule libraries to identify potential therapeutics for psychostimulant abuse, 3-hydroxy-2-(3-hydroxyphenyl)-4H-1-benzopyran-4-ones were shown to be isoform-selective PKC-zeta inhibitors. ... Full text Link to item Cite

Thermodynamic characterization of iron(III) and zinc binding by Brasilibactin A

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

Analysis of HIF-1 inhibition by manassantin A and analogues with modified tetrahydrofuran configurations.

Journal Article Bioorg Med Chem Lett · July 15, 2009 We have shown that manassantin A downregulated the HIF-1alpha expression and inhibited the secretion of VEGF. We have also demonstrated that the 2,3-cis-3,4-trans-4,5-cis-configuration of the tetrahydrofuran is critical to the HIF-1 inhibition of manassant ... Full text Link to item Cite

The end game of chemical genetics: target identification.

Journal Article Future medicinal chemistry · July 2009 The use of classical genetic and molecular biology methods along with the sequencing of many genomes has proven crucial for elucidating complex biological processes. Despite being invaluable tools, their limitations have led to a search for more versatile ... Full text Cite

A small molecule inhibitor of alpha4 integrin-dependent cell migration.

Journal Article Bioorganic & medicinal chemistry · February 2009 A small molecule inhibitor of alpha4 integrin-dependent cell migration was identified through a cell-based screen of small molecule libraries. Biochemical and cellular experiments suggest that this molecule functions by interacting with gamma-parvin. This ... Full text Cite

Stereoselective synthesis and osteogenic activity of subglutinols A and B

Journal Article Journal of the American Chemical Society · 2009 Cite

Nucleophilic addition of organozinc reagents to 2-sulfonyl cyclic ethers: stereoselective synthesis of manassantins A and B.

Journal Article Org Lett · January 1, 2009 A convergent route to the synthesis of manassantins A and B, potent inhibitors of HIF-1, is described. Central to the synthesis is a stereoselective addition of an organozinc reagent to a 2-benzenesulfonyl cyclic ether to achieve the 2,3-cis-3,4-trans-4,5- ... Full text Link to item Cite

ORGN 523-Total synthesis of largazole

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 17, 2008 Link to item Cite

Total synthesis and molecular target of largazole, a histone deacetylase inhibitor.

Journal Article Journal of the American Chemical Society · July 2008 Full details of the concise and convergent synthesis (eight steps, 19% overall yield), its extension to the preparation of a series of key analogues, and the molecular target and pharmacophore of largazole are described. Central to the synthesis of largazo ... Full text Cite

Synthesis of brasilibactin A and confirmation of absolute configuration of β-hydroxy acid fragment

Journal Article Tetrahedron Letters · November 12, 2007 A synthesis of brasilibactin A, a cytotoxic siderophore from the actinomycete of Nocardia brasiliensis, and three unnatural diastereomers of the natural product is described. Four possible diastereomers of the β-hydroxy acid fragment were prepared via asym ... Full text Cite

A small-molecule antagonist of the hedgehog signaling pathway.

Journal Article Chembiochem : a European journal of chemical biology · November 2007 Full text Cite

Stereoselective synthesis of tetrahydrofuran lignans via BF(3) x OEt(2)-promoted reductive deoxygenation/epimerization of cyclic hemiketal: synthesis of (-)-odoratisol C, (-)-futokadsurin A, (-)-veraguensin, (+)-fragransin A(2), (+)-galbelgin, and (+)-talaumidin.

Journal Article Organic letters · September 2007 A versatile route to the synthesis of 2,5-diaryl-3,4-dimethyltetrahydrofuran lignans, (-)-odoratisol C (1), (-)-futokadsurin A (2), (-)-veraguensin (3), (+)-fragransin A2 (4), (+)-galbelgin (5), and (+)-talaumidin (6), is described. Central to the synthesi ... Full text Cite

A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase.

Journal Article Proceedings of the National Academy of Sciences of the United States of America · March 2006 Cell motility is a complex biological process, involved in development, inflammation, homeostasis, and pathological processes such as the invasion and metastatic spread of cancer. Here, we describe a genomic screen designed to identify inhibitors of cell m ... Full text Cite

First synthesis and structural elucidation of (-)-presphaerene.

Journal Article The Journal of organic chemistry · September 2004 The first total synthesis of (-)-presphaerene (1) was achieved from (R)-glyceraldehyde 9 in 19 steps, demonstrating the novel "folding and allylic strain-controlled" intramolecular ester enolate S(N)2' alkylation strategy could be extended to the stereosel ... Full text Cite

Asymmetric total synthesis of ent-(-)-roseophilin: assignment of absolute configuration.

Journal Article Journal of the American Chemical Society · September 2001 An asymmetric total synthesis of ent-(-)-roseophilin (1), the unnatural enantiomer of a novel naturally occurring antitumor antibiotic, is described. The approach enlists a room temperature heterocyclic azadiene inverse electron demand Diels-Alder reaction ... Full text Cite

Total synthesis of phomazarin

Journal Article Journal of the American Chemical Society · March 24, 1999 A concise total synthesis of phomazarin (1) is detailed enlisting a heterocyclic azadiene inverse electron demand Diels-Alder reaction (1,2,4- triazine → pyridine) for preparation of the fully substituted and appropriately functionalized pyridine C-ring. T ... Full text Cite

Total synthesis of nothapodytine b and (-)-mappicine

Journal Article Journal of the American Chemical Society · February 18, 1998 Concise total syntheses of naturally occurring nothapodytine B (1, mappicine ketone) and ( - )-mappicine (3) are detailed. The approach is based on the implememation of a room-temperature, inverse electron demand Diels-Alder reaction of the N-sulfonyl-1-az ... Full text Cite

An asymmetric synthesis of (+)-isonitramine by 'triple allylic strain-controlled' intramolecular SN2' alkylation

Journal Article Tetrahedron Letters · February 26, 1996 The spirocyclic alkaloid (+)-isonitramine (1) has been synthesized in a stereoselective manner utilizing a novel 'triple allylic strain-controlled' intramolecular lactam enolate SN2' alkylation. ... Full text Cite