Title:Multivalent Agents: A Novel Concept and Preliminary Practice in Anti-HIV Drug Discovery
VOLUME: 20 ISSUE: 6
Author(s):Yu'ning Song, Peng Zhan, Xiao Li, Diwakar Rai, Erik De Clercq and Xinyong Liu
Affiliation:Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, P.R. China.
Keywords:HIV, AIDS, multivalency/polyvalency approach, drug design, chemical space, “mixed sites inhibitor”
Abstract:The term multivalency (polyvalency) in the biological science is defined as the simultaneous binding of multiple ligands to
one receptor (or multiple receptors to one ligand). The possibility of gaining potency and selectivity was significantly increased through
the use of multivalent ligand as a homo- or hetero-dimer, thus multivalent ligands provided a more attractive strategy to design novel
anti-HIV agents with therapeutic applications. Moreover, similar to phenomenon of multivalency, an alternative strategy is called the
“mixed sites inhibitor”, viz. a single molecule that possesses enough chemical space to maximize interactions with its complementary
binding pocket, or to bind simultaneously in more than one regions in a target. Actually, the addition of a third heterocyclic nucleus to the
parent compound resulted in “mixed sites” anti-HIV agents with broad spectrum of activities against the mutant HIV-1 strains. Based on
current representative examples, the present article provided a brief review on the rationale for the design of different classes of multivalency
anti-HIV agents and also discussed the advantages over their monomeric counterparts, providing a novel paradigm to facilitate the
development of anti-HIV/AIDS therapeutic agents in treatment of HIV infected community.
