期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 57, 期 31, 页码 9655-9659出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201802983
关键词
cytokines; drug discovery; glycolipids; immunology; ligand design
资金
- JSPS KAKENHI [JP26282211, JP17H02207, JP17H05800, JP16H01162, JP16K16638]
- AMED [JP18ak0101072]
- Mizutani Foundation for Glycoscience
- Mishima Kaiun Memorial Foundation
- Takeda Science Foundation
Th2-biasing CD1d ligands are attractive potential candidates for adjuvants and therapeutic drugs. However, the number of potent ligands is limited, and their biasing mechanism remain unclear. Herein, a series of novel Th2-biasing CD1d glycolipid ligands, based on modification of their lipid part, have been identified. These have shown high binding affinities and efficient Th2 cytokine production. Importantly, the truncated acyl chain containing variants still retain their binding affinities and agonistic activities, which can be associated with an anchoring effect, that is, formation of a buried hydrogen bond between a polar group on the acyl chain and the CD1d lipid-binding pocket. The analysis indicated that the appearance rates of ligand-CD1d complexes on the cell surface were involved in Th2-biasing responses. The designed ligands, having the anchor in the shorter lipid part, are one of the most potent Th2-biasing ligands among the known ligands.
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