2013年12月18日
Total synthesis and anti-hepatitis C virus activity of MA026
Journal of the American Chemical Society
- 巻
- 135
- 号
- 50
- 開始ページ
- 18949
- 終了ページ
- 18956
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/ja410145x
- 出版者・発行元
- 50
The first total synthesis of MA026 and the identification of its candidate target protein for anti-hepatitis C virus activity are presented. MA026, a novel lipocyclodepsipeptide isolated from the fermentation broth of Pseudomonas sp. RtIB026, consists of a cyclodepsipeptide, a chain peptide, and an N-terminal (R)-3-hydroxydecanoic acid. The first subunit, side chain 2, was prepared by coupling fatty acid moiety 4 with tripeptide 5. The key macrocyclization of the decadepsipeptide at l-Leu10-d-Gln11 provided the second subunit, cyclodepsipeptide 3. Late-stage condensation of the two key subunits and final deprotection afforded MA026. This convergent, flexible, solution-phase synthesis will be invaluable in generating MA026 derivatives for future structure-activity relationship studies. An infectious hepatitis C virus (HCV) cell culture assay revealed that MA026 suppresses HCV infection into host hepatocytes by inhibiting the entry process in a dose-dependent manner. Phage display screening followed by surface plasmon resonance (SPR) binding analyses identified claudin-1, an HCV entry receptor, as a candidate target protein of MA026. © 2013 American Chemical Society.
- ID情報
-
- DOI : 10.1021/ja410145x
- ISSN : 0002-7863
- ISSN : 1520-5126
- PubMed ID : 24251365
- SCOPUS ID : 84890620194