Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 9655-9659 |
| Number of pages | 5 |
| Journal | Angewandte Chemie - International Edition |
| Volume | 57 |
| Issue number | 31 |
| DOIs | |
| Publication status | Published - 2018 Jul 26 |
Fingerprint
Keywords
- cytokines
- drug discovery
- glycolipids
- immunology
- ligand design
ASJC Scopus subject areas
- Catalysis
- Chemistry(all)
Cite this
Potent Th2 Cytokine Bias of Natural Killer T Cell by CD1d Glycolipid Ligands : Anchoring Effect of Polar Groups in the Lipid Component. / Inuki, Shinsuke; Kashiwabara, Emi; Hirata, Natsumi; Kishi, Junichiro; Nabika, Etsuko; Fujimoto, Yukari.
In: Angewandte Chemie - International Edition, Vol. 57, No. 31, 26.07.2018, p. 9655-9659.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Potent Th2 Cytokine Bias of Natural Killer T Cell by CD1d Glycolipid Ligands
T2 - Anchoring Effect of Polar Groups in the Lipid Component
AU - Inuki, Shinsuke
AU - Kashiwabara, Emi
AU - Hirata, Natsumi
AU - Kishi, Junichiro
AU - Nabika, Etsuko
AU - Fujimoto, Yukari
PY - 2018/7/26
Y1 - 2018/7/26
N2 - 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.
AB - 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.
KW - cytokines
KW - drug discovery
KW - glycolipids
KW - immunology
KW - ligand design
UR - http://www.scopus.com/inward/record.url?scp=85050501087&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050501087&partnerID=8YFLogxK
U2 - 10.1002/anie.201802983
DO - 10.1002/anie.201802983
M3 - Article
C2 - 29863807
AN - SCOPUS:85050501087
VL - 57
SP - 9655
EP - 9659
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 31
ER -