Identification of minimal sequence for HIV-1 fusion inhibitors.

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.

• Authors: 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
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 16 Issue 20 Pg. 9184-7 (Oct 15 2008) ISSN: 1464-3391 [Electronic] England
• PMID: 18819810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HIV Fusion Inhibitors

Topics

• Amino Acid Sequence
• Cell Line
• Circular Dichroism
• HIV Fusion Inhibitors (chemistry, pharmacology)
• HIV-1 (drug effects)
• Humans
• Molecular Sequence Data
• Protein Denaturation