A unidirectional crosslinking strategy for HIV-1 protease dimerization inhibitors

Abstract

A novel strategy to identify potent HIV-1 protease dimerization inhibitors was developed using 12-aminododecanoic acid as a tether to crosslink interfacial peptides. The directionality of the southern peptide was changed from N → C to C → N as compared to previously reported inhibitors. The terminal amine of the southern peptide and side chains were further diversified to find essential functional groups for dimerization inhibition of HIV-1 protease.