Identification of minimal sequence for HIV-1 fusion inhibitors

Emergence of multi-drug resistant HIV-1 is a serious problem for AIDS treatment. Recently, the virus-cell membrane fusion process has been identified as a promising target for the development of novel drugs against these resistant variants. In this study, we identified a 29-residue peptide fusion inhibitor, SC29EK, which shows activity comparable to the previously reported inhibitor SC35EK. Some residues in SC29EK not required for interaction with virus gp41 heptad repeat 1 (HR1) were replaced with a non-proteinogenic amino acid, 2-aminoisobutyric acid (Aib), to stabilize the α-helix structure and to provide resistance to peptidases.

Minimal sequence of potential HIV-1 fusion inhibitors was identified using glycoprotein gp41-derived peptides containing α-helix-inducible EK motifs. One of the N-terminal motifs was replaced with an α-helix-inducible motif containing 2-aminoisobutyric acids.Figure optionsDownload as PowerPoint slide