Design of a novel HIV-1 fusion inhibitor that displays a minimal interface for binding affinity.
Reported herein are the design, biological activities, and biophysical properties of a novel HIV-1 membrane fusion inhibitor. alpha-Helix-inducible X-EE-XX-KK motifs were applied to design an enfuvirtide analogue 2 that exhibited highly potent anti-HIV activity against wild-type HIV-1, enfuvirtide-resistant HIV-1 strains, and an HIV-2 strain in vitro. Indispensable residues for bioactivity of enfuvirtide, including the residues interacting with the N-terminal heptad repeat and the C-terminal hydrophobic residues, were identified.
Oishi
Shinya
S
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. soishi@pharm.kyoto-u.ac.jp
Ito
Saori
S
Nishikawa
Hiroki
H
Watanabe
Kentaro
K
Tanaka
Michinori
M
Ohno
Hiroaki
H
Izumi
Kazuki
K
Sakagami
Yasuko
Y
Kodama
Eiichi
E
Matsuoka
Masao
M
Fujii
Nobutaka
N
D000595:Amino Acid Sequence; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D010446:Peptide Fragments; D000077560:Enfuvirtide