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 alpha-helix structure and to provide resistance to peptidases.
Nishikawa
Hiroki
H
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Oishi
Shinya
S
Fujita
Mizuno
M
Watanabe
Kentaro
K
Tokiwa
Rei
R
Ohno
Hiroaki
H
Kodama
Eiichi
E
Izumi
Kazuki
K
Kajiwara
Keiko
K
Naitoh
Takeshi
T
Matsuoka
Masao
M
Otaka
Akira
A
Fujii
Nobutaka
N
D000595:Amino Acid Sequence; D002460:Cell Line; D002942:Circular Dichroism; D023581:HIV Fusion Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D011489:Protein Denaturation
D023581:HIV Fusion Inhibitors