Palmitic acid analogs exhibit nanomolar binding affinity for the HIV-1 CD4 receptor and nanomolar inhibition of gp120-to-CD4 fusion.

ABSTRACT:

Background

We recently reported that palmitic acid (PA) is a novel and efficient CD4 fusion inhibitor to HIV-1 entry and infection. In the present report, based on in silico modeling of the novel CD4 pocket that binds PA, we describe discovery of highly potent PA analogs with increased CD4 receptor binding affinities (K(d)) and gp120-to-CD4 inhibition constants (K(i)). The PA analogs were selected to satisfy Lipinski's rule of drug-likeness, increased solubility, and to avoid potential cytotoxicity.

Principal findings

PA analog 2-bromopalmitate (2-BP) was most efficacious with K(d) approximately 74 nM and K(i) approximately 122 nM, ascorbyl palmitate (6-AP) exhibited slightly higher K(d) approximately 140 nM and K(i) approximately 354 nM, and sucrose palmitate (SP) was least

SUBMITTER: Paskaleva EE 

PROVIDER: S-EPMC2921400 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature