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Identification of minimal sequence for HIV-1 fusion inhibitors
Authors:Nishikawa Hiroki  Oishi Shinya  Fujita Mizuno  Watanabe Kentaro  Tokiwa Rei  Ohno Hiroaki  Kodama Eiichi  Izumi Kazuki  Kajiwara Keiko  Naitoh Takeshi  Matsuoka Masao  Otaka Akira  Fujii Nobutaka
Affiliation:Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
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.
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