Zhengqiang Wang, Ph.D.

Assistant Professor, Center for Drug Design
Assistant Director, Center for Drug Design

Contact information
 
Office: 7-228 Phillips Wangensteen
Phone: 612-626-7025
Fax: 612-625-8154
E-mail: wangx472@umn.edu

Education
 
B.S., Nankai University, China, 1993
M.S., Peking University, China, 1996
Ph.D., Wayne State University, 2003

Research Interest

Research in our group is centered at the discovery and the development of novel antivirals for the treatment of HIV / AIDS and hepatitis C. We are particularly interested in targeting HIV entry, reverse transcriptase (polymerase and RNase H), integrase and HCV NS5B polymerase. The major thrust of our efforts in anti-HIV research is to fight resistant mutants. Towards this end, we are exploring three distinct strategies: 1) studying viral and cellular pathways that could potentially be utilized us novel intervention targets; 2) identifying novel chemotypes capable of inhibiting validated therapeutic targets (HIV interase and RNase H, HCV polymerase) by combing virtual screening (collaboration with Dr. Sham) and organic synthesis; and 3) developing novel dual inhibitors combining known pharmacophores that could accommodate activities against two important HIV enzymes (collaboration with Dr. Vince). 

Dual Inhibitors in HIV Chemotherapy

Due to the lack of HIV vaccines and the existence of viral reservoirs, HIV/AIDS is neither preventable nor curable. Chemotherapy, especially highly active antiretroviral therapy (HAART), remains the only means to manage this disease. Clinical studies have demonstrated that the success of HAART requires nearly perfect patient adherence, which is extremely difficult to achieve due to complex dosing and severe side effects associated with drug cocktails. We are committed to developing simplified multi-target therapy to address these long-standing issues. We expect that by combining two distinct pharmacophores into a compact molecule, we could generate a bifunctional inhibitor that simultaneously engages two virally encoded enzymes, e.g. reverse transcriptase (RT) and integrase (IN). Such a dual inhibitor would still be able to contain resistant viral strains while alleviating issues of complex dosing and side-effects. In our study, a structure-based rational design strategy is employed to generate molecular scaffolds that can accommodate high affinity for both enzymes. A schematic illustration is shown in Figure 1.

Selected Publications

Design and Synthesis of HIV Reverse Transcriptase and Integrase: Introducing a Diketoacid Functionality into Delavirdine. Wang Z, Vince, R. Bioorg. Med. Chem. 2008, 16, 3587-3595. Abstract

Synthesis of Pyrimidine and Quinolone Conjugates as a Scaffold for Dual Inhibitors of HIV Reverse Transcriptase and Integrase. Wang Z, Vince R. Bioorg. Med. Chem. Lett. 2008, 18, 1293-1296.  Abstract

Rationally Designed Dual Inhibitors of HIV Reverse Transcriptase and Integrase. Wang Z, Bennett EM, Wilson DJ, Salomon C, Vince R. J. Med. Chem. 2007, 50, 3416.  Abstract

Synthesis of Highly Substituted Cyclopentenones via the [4 + 1] Cycloaddition of Nucleophilic Carbenes and Vinyl Ketenes. Rigby JH, Wang Z. Org. Lett. 2003, 5, 263.  Abstract    

[4 + 1] Cycloaddition of N-Heterocyclic Carbenes with Vinyl Isocyanates. Rigby JH, Wang Z. Org. Lett. 2002, 4, 4289.  Abstract  

Poster

From RT Inhibitor to RT / IN Dual Inhibitor: A Rational Design - Wang and Vince