Peptide bond mimicry by (E)-alkene and (Z)-fluoroalkene peptide isosteres: synthesis and bioevaluation of alpha-helical anti-HIV peptide analogues.
The alpha-helix structures of the anti-HIV fusion inhibitory peptides are stabilized by the amino acid sequence and by intrachain hydrogen bonds. The study of peptide analogues using (E)-alkene and (Z)-fluoroalkene dipeptide isosteres demonstrated the substantial, yet position-dependent, contribution of hydrogen bonds to the alpha-helix stability and anti-HIV bioactivity.
Oishi
Shinya
S
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. soishi@pharm.kyoto-u.ac.jp
Kamitani
Hirotaka
H
Kodera
Yasuyo
Y
Watanabe
Kentaro
K
Kobayashi
Kazuya
K
Narumi
Tetsuo
T
Tomita
Kenji
K
Ohno
Hiroaki
H
Naito
Takeshi
T
Kodama
Eiichi
E
Matsuoka
Masao
M
Fujii
Nobutaka
N
D000475:Alkenes / Q000737:chemistry*; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D032701:Biomimetics; D005461:Fluorine / Q000737:chemistry*; D006678:HIV / Q000187:drug effects*; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D000475:Alkenes; D019380:Anti-HIV Agents; D010455:Peptides; D005461:Fluorine