Novel strategies for targeting the dimerization interface of HIV protease with cross-linked interfacial peptides.

As the prevalence of AIDS continues to grow, and current therapeutic agents begin to lose efficacy, the need for alternative treatments to combat HIV has become significantly greater. Targeting the highly conserved dimerization interface of HIV protease (PR) with interfacial peptides has been shown to reduce the activity of the enzyme due to generation of inactive monomers. The potency of these peptide-based inhibitors has been dramatically increased by cross-linking the interfacial sequences derived from HIV PR. This review focuses on a variety of strategies to develop potent, low-molecular-weight dimerization inhibitors of HIV PR. Copyright 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 126-133, 2002