Identification of minimal sequence for HIV-1 fusion inhibitors

Hiroki Nishikawa; Shinya Oishi; Mizuno Fujita; Kentaro Watanabe; Rei Tokiwa; Hiroaki Ohno; Eiichi Kodama; Kazuki Izumi; Keiko Kajiwara; Takeshi Naitoh; Masao Matsuoka; Akira Otaka; Nobutaka Fujii

doi:10.1016/j.bmc.2008.09.018

Identification of minimal sequence for HIV-1 fusion inhibitors

Bioorg Med Chem. 2008 Oct 15;16(20):9184-7. doi: 10.1016/j.bmc.2008.09.018. Epub 2008 Sep 10.

Authors

Hiroki Nishikawa¹, Shinya Oishi, Mizuno Fujita, Kentaro Watanabe, Rei Tokiwa, Hiroaki Ohno, Eiichi Kodama, Kazuki Izumi, Keiko Kajiwara, Takeshi Naitoh, Masao Matsuoka, Akira Otaka, Nobutaka Fujii

Affiliation

¹ Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

PMID: 18819810
DOI: 10.1016/j.bmc.2008.09.018

Abstract

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 alpha-helix structure and to provide resistance to peptidases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Cell Line
Circular Dichroism
HIV Fusion Inhibitors / chemistry*
HIV Fusion Inhibitors / pharmacology*
HIV-1 / drug effects
Humans
Molecular Sequence Data
Protein Denaturation

Substances

HIV Fusion Inhibitors