Abstract

. Dr. Cheng proposes to study the biochemical pharmacology of anti-HIV nucleosides. The project aims to clarify key cellular biochemical determinants that play a key role in the action, resistance, and toxicity of anti-HIV nucleoside analogs. The proposed two specific aims are: (1) Purification and characterization of a cytoplasmic DNA exonuclease that may constitute a major mechanism of viral resistance to anti-HIV 1 nucleoside analogs; (2) Isolation and characterization of mitochondrial deoxynucleoside triphosphate (dNTP) carrier that may be a significant determinant in the toxicity of anti-HIV-1 nucleoside analogs to mitochondrial function. The investigator believes that the proposed studies should be useful in better understanding the pharmacology of anti-HIV- 1 analogs, new drug discovery, and the improvement of therapy with currently approved nucleoside analogs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI038204-03S1
Application #
2863865
Study Section
AIDS and Related Research Study Section 4 (ARRD)
Project Start
1995-07-01
Project End
1998-08-31
Budget Start
1997-07-01
Budget End
1998-08-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Wang, Ying; Chen, Shao-Ru; Yang, Xiaoming et al. (2018) Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents. Bioorg Med Chem 26:630-636
Wang, Ying; Lam, Wing; Chen, Shao-Ru et al. (2016) Tylophorine Analog DCB-3503 Inhibited Cyclin D1 Translation through Allosteric Regulation of Heat Shock Cognate Protein 70. Sci Rep 6:32832
Tsao, Ning; Lee, Ming-Hsiang; Zhang, Wei et al. (2015) The contribution of CMP kinase to the efficiency of DNA repair. Cell Cycle 14:354-63
Wu, Chien-Huang; Wang, Chuan-Jen; Chang, Chun-Ping et al. (2015) Function-oriented development of CXCR4 antagonists as selective human immunodeficiency virus (HIV)-1 entry inhibitors. J Med Chem 58:1452-65
Fan, Jiyun; Wang, Ying; Xiong, Hui et al. (2014) Impact of the rtI187V polymerase substitution of hepatitis B virus on viral replication and antiviral drug susceptibility. J Gen Virol 95:2523-30
Selvaraj, S; Ghebremichael, M; Li, M et al. (2014) Antiretroviral therapy-induced mitochondrial toxicity: potential mechanisms beyond polymerase-? inhibition. Clin Pharmacol Ther 96:110-20
Haraguchi, Kazuhiro; Takeda, Shingo; Kubota, Yutaka et al. (2013) From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir. Curr Pharm Des 19:1880-97
Tsou, Lun K; Cheng, Yao; Cheng, Yung-Chi (2012) Therapeutic development in targeting protein-protein interactions with synthetic topological mimetics. Curr Opin Pharmacol 12:403-7
Tsou, Lun K; Chen, Chin-Ho; Dutschman, Ginger E et al. (2012) Blocking HIV-1 entry by a gp120 surface binding inhibitor. Bioorg Med Chem Lett 22:3358-61
Haraguchi, Kazuhiro; Shimada, Hisashi; Kimura, Keiogo et al. (2011) Synthesis of 4'-Ethynyl-2'-deoxy-4'-thioribonucleosides and Discovery of a Highly Potent and Less Toxic NRTI. ACS Med Chem Lett 2:692-697

Showing the most recent 10 out of 32 publications