Education and Experience
1983-1987 B.S. Chemistry, Zhejiang Normal University, China.
1987-1990 M.S. Organic Chermistry, Shanghai Institute of Materia Medica, China.
1994-1999 Ph.D. Medicinal Chemistry, The University of Tennessee, U.S.A.
1999-2002 Post-doctoral Fellow, Biochemistry (especially Enzymology), The Johns Hopkins University School of Medicine, U.S.A.
2002-2004 Research Associate, Biochemistry (especially Enzymology), The Johns Hopkins University School of Medicine, U.S.A.
2004-2011 The James L. and Martha J. Foght Assistant Professor (tenure-track), The University of Akron, Department of Chemistry, U.S.A.
2007-2011 Participating faculty, Integrated Bioscience Ph.D. Program, The University of Akron, U.S.A.
2012-present Professor, Jiangsu University, School of Pharmacy, China.
Research Interests
Medicinal Chemistry:To develop catalytic mechanism-based enzyme inhibitors; to develop activity-based chemical probes for enzyme-catalyzed reactions and to explore the applications of the developed probes in biology and medicinal chemistry; to develop novel “peptide stapling” methodologies and to explore the applications of the developed methodologies in medicinal chemistry.
In line with these research interests, my research group while at University of Akron, the United States, was the first in the world to start developing the catalytic mechanism-based inhibitors for the deacylation reaction catalyzed by the physiologically and biomedically very important sirtuin family of protein acyl-lysine deacylase enzymes, with the identification of the prototypes respectively for the three major types of the catalytic mechanism-based sirtuin inhibitory warheads (i.e. the thioacyl-type, the thiourea-type, and the carboxamide-type). Moreover, in recent years my research group has succeeded in identifying the up-to-date most potent and/or selective, proteolytically stable, and cell permeable sirtuin inhibitors (Ref:Jiang, Yanhong; Liu, Jiajia; Chen, Di; Yan, Lingling; Zheng, Weiping*. Sirtuin inhibition: strategies, inhibitors, and therapeutic potential.Trends in Pharmacological Sciences2017,38, 459-472).Perthe up-to-date studies, the catalytic mechanism-based design represents the simplest yet most efficacious approach to generating the sirtuin inhibitory lead compounds. As an indication of my research group’s academic standing in the fields of sirtuin chemical biology, sirtuin bioorganic chemistry, and sirtuin medicinal chemistry, I was invited to edit the volume ofSirtuins in Health and Diseasefor Elsevier’sProgress in Molecular Biology and Translational Science(https://www.sciencedirect.com/science/bookseries/18771173, published in February, 2018).
In collaboration with Prof. Zhenghe Wang’s research group (Case Western Reserve University, the United States), we recently identified a protein-protein interaction (PPI) uniquely present in certain colon cancer cells, which represents a novel target for developing anti-colon cancer therapeutics (Ref:Hao, Yujun; Wang, Chao; Cao, Bo; Hirsch, Brett M.; Song, Jing; Markowitz, Sanford D.; Ewing, Rob M.; Sedwick, David; Liu, Lili; Zheng, Weiping*; Wang, Zhenghe*. Gain of interaction with IRS1 by p110alpha helical domain mutants is crucial for their oncogenic functions.Cancer Cell2013,23, 583-593;Commentary:John E. Burke and Roger L. Williams (MRC Laboratory of Molecular Biology, Cambridge, UK). Connecting with an old partner in a new way.Cancer Cell2013,23, 559-561). While a stapled peptide constructed by the known all-hydrocarbon “peptide stapling” approach was identified in this study to be a potent and cell permeable inhibitor of this PPI, we intended to develop novel superior “peptide stapling” methodologies and to explore the applications of the developed methodologies in this particular case and in medicinal chemistry in general.
The research in my group has far-reaching impact toward developing novel therapeutic agents for human diseases especially cancer. The participation in the research in my group would be able to instill in a researcher a deep appreciation of the concepts/principles of modern medicinal chemistry and to get equipped with research techniques in modern medicinal chemistry.
Representative peer-reviewed publications (*denotes corresponding author)
Hu, Xiao;Zheng, Weiping*.Chemical probes in sirtuin research. InProgress in Molecular Biology and Translational Science,2018, Volume 154 (Sirtuins in Health and Disease, Edited byWeiping Zheng), Pages 1-24.
Li, Shengchao;Zheng, Weiping*.Mammalian sirtuins SIRT4 and SIRT7. InProgress in Molecular Biology and Translational Science,2018, Volume 154 (Sirtuins in Health and Disease, Edited byWeiping Zheng), Pages 147-168.
Hu, Xiao; He, Yanhua; Wu, Liping; Hao, Yujun; Wang, Zhenghe; Zheng, Weiping*.Novel all-hydrocarbon stapled p110alpha[E545K] peptides as blockers of the oncogenic p110alpha[E545K]-IRS1 interaction.Bioorganic & Medicinal Chemistry Letters2017,27, 5446-5449.
Mukhtar, Yusif M.; Huang, Yajun; Liu, Jiajia; Chen, Di;Zheng, Weiping*.Acetanilide and bromoacetyl-lysine derivatives as activators for human histone deacetylase 8.Bioorganic & Medicinal Chemistry Letters2017,27, 2319-2323.
Jiang, Yanhong; Liu, Jiajia; Chen, Di; Yan, Lingling;Zheng,Weiping*.Sirtuin inhibition: strategies, inhibitors, and therapeutic potential.TrendsinPharmacologicalSciences2017,38, 459-472. (Invited)
Wang, Juan; Zang, Wenwen; Liu, Jiajia; Zheng, Weiping*.Bivalent SIRT1 inhibitors.Bioorganic & Medicinal Chemistry Letters2017,27, 180-186.
Chen, Di; Zheng, Weiping*.Cyclic peptide-based potent and selective SIRT1/2 dual inhibitors harboring N(epsilon)-thioacetyl-lysine.Bioorganic & Medicinal Chemistry Letters2016,26, 5234-5239.
Liu, Jiajia; Huang, Yajun; Zheng, Weiping*.A selective cyclic peptidic human SIRT5 inhibitor.Molecules2016,21, 1217.
Liu, Jiajia; Zheng, Weiping*.Cyclic peptide-based potent human SIRT6 inhibitors.Organic & Biomolecular Chemistry2016,14, 5928-5935.
Huang, Yajun; Liu, Jiajia; Yan, Lingling; Zheng Weiping*.Simple N(epsilon)-thioacetyl- lysine-containing cyclic peptides exhibiting highly potent sirtuin inhibition.Bioorganic & Medicinal Chemistry Letters2016,26, 1612-1617.
He, Yanhua; Yan, Lingling; Zang, Wenwen; Zheng, Weiping*.Novel sirtuin inhibitory warheads derived from the N(epsilon)-acetyl-lysine analog L-2-amino-7-carboxamidoheptanoic acid.Organic & Biomolecular Chemistry2015,13, 10442-10450.
Chen, Bing; Wang, Juan; Huang, Yajun; Zheng, Weiping*.Human SIRT3 tripeptidic inhibitors containing N(epsilon)-thioacetyl-lysine.Bioorganic & Medicinal Chemistry Letters2015,25, 3481-3487.
Zang, Wenwen; Hao, Yujun; Wang, Zhenghe; Zheng, Weiping*.Novel thiourea-based sirtuin inhibitory warheads.Bioorganic & Medicinal Chemistry Letters2015,25, 3319-3324.
Chen, Bing; Zang, Wenwen; Wang, Juan; Huang, Yajun; He, Yanhua; Yan, Lingling; Liu, Jiajia; Zheng, Weiping*.The chemical biology of sirtuins.Chemical Society Reviews2015,44, 5246-5264. (Invited)
He, Yanhua; Chen, Di; Zheng, Weiping*.An enhanced functional interrogation/ manipulation of intracellular signaling pathways with the peptide “stapling” technology.Oncogene2015,34, 5685-5698. (Invited)
Zheng, Weiping*; Huang, Yajun. The chemistry and biology of the alpha-ketoglutarate- dependent histone N(epsilon)-methyl-lysine demethylases.MedChemComm2014, 5, 297-313. (Invited for the themed issue onChemical Biology for Target Identification and Validation, guest edited byProf.Nathanael Gray(Harvard University, U.S.A.) andDr.Lyn Jones(Pfizer, Cambridge, U.S.A.).
Zheng, Weiping*.Sirtuins as emerging anti-parasitic targets.European Journal of Medicinal Chemistry2013,59, 132-140. (Invited)
Hao, Yujun; Wang, Chao; Cao, Bo; Hirsch, Brett M.; Song, Jing; Markowitz, Sanford D.; Ewing, Rob M.; Sedwick, David; Liu, Lili;Zheng, Weiping*;Wang, Zhenghe*. Gain of interaction with IRS1 by p110alpha helical domain mutants is crucial for their oncogenic functions.Cancer Cell2013,23, 583-593. (Comment by John E. Burke and Roger L. Williams (MRC Laboratory of Molecular Biology, Cambridge, UK) in: Connecting with an old partner in a new way.Cancer Cell2013,23, 559-561)
Hirsch, Brett M.; Hao, Yujun; Li, Xiaopeng; Wesdemiotis, Chrys; Wang, Zhenghe;Zheng, Weiping*.A mechanism-based potent sirtuin inhibitor containing N(epsilon)-thiocarbamoyl-lysine (TuAcK).Bioorganic & Medicinal Chemistry Letters2011,21, 4753-4757.
Hirsch, Brett M.; Du, Zhanwen; Li, Xiaopeng; Sylvester, Jorge A.; Wesdemiotis, Chrys; Wang, Zhenghe;Zheng, Weiping*.Potent sirtuin inhibition bestowed by L-2-amino-7-carboxamidoheptanoic acid (L-ACAH), a N(epsilon)-acetyl-lysine analog.MedChemComm2011,2, 291-299.
Fatkins, David G.; Monnot, Andrew D.;Zheng, Weiping*.N(epsilon)-thioacetyl-lysine: a multi-facet functional probe for enzymatic protein lysine N(epsilon)-deacetylation.Bioorganic & Medicinal Chemistry Letters2006,16, 3651-3656.
Contacts
E-mail:wzheng@ujs.edu.cn
Mailing Address: School of Pharmacy, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, P. R. China
