2010年10月
Affinity selection and sequence-activity relationships of HIV-1 membrane fusion inhibitors directed at the drug-resistant variants
MEDCHEMCOMM
- 巻
- 1
- 号
- 4
- 開始ページ
- 276
- 終了ページ
- 281
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1039/c0md00091d
- 出版者・発行元
- ROYAL SOC CHEMISTRY
Enfuvirtide is the first approved membrane fusion inhibitor against HIV-1. Although this drug is effective against multi-drug resistant strains, the emergence of enfuvirtide-resistant strains has been reported in patients who have received an enfuvirtide-containing regimen. Based on the high affinity of synthetic HIV-1 gp41 C-terminal heptad repeat (C-HR) peptides to the counterpart trimeric N-terminal heptad repeat (N-HR) coiled-coil structure, a novel screening approach has been established to facilitate the identification of potent fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1. In this process, affinity selection using histidine-tagged N-HR peptides with the sequences derived from wild-type and resistant strains efficiently captured potent inhibitory peptides from a pool of highly water-soluble C-HR peptides with a-helix-inducible motifs. A highly potent peptide was found from a single amino acid substitution observed in an enfuvirtide-resistant variant as well as peptides with unprecedented modifications at the mutated site.
- リンク情報
- ID情報
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- DOI : 10.1039/c0md00091d
- ISSN : 2040-2503
- CiNii Articles ID : 120002484932
- Web of Science ID : WOS:000284980100004