期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 135, 期 50, 页码 18949-18956出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja410145x
关键词
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资金
- Toyo Suisan Kaisha, LTD.
- ADEKA Corporation
- Sasalcawa Scientific Research Grant from The Japan Science Society
- Ministry of Health, Labor, and Welfare, Japan
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [24102537] Funding Source: KAKEN
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-Leu(10)-D-Gln(11) 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.
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