Small molecule dimerization inhibitors of HIV protease
Jean Chmielewski
Department of Chemistry
Purdue University
As more information on macromolecular structure unfolds, it has become
obvious that interprotein interactions are a ubiquitous and fundamental
aspect of biological activity. Whereas the nature of these protein-protein
interactions is becoming better understood, rational approaches to
inhibiting these interactions are still in their infancy.
Using dimeric HIV-1 protease as a template, we have developed a strategy to inhibit
dimerization based on the crosslinking of interfacial peptides derived from
the protease. In the current study, we endeavor to identify the essential
residues of a crosslinked, interfacial peptide inhibitor of HIV-1 protease,
and obtain a minimal structure that maintains the essential features of
dimerization inhibition.