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Improved Th17 Selectivity of ?-Galactosylceramide via Noncovalent Interactions with Diether Moiety.

ABSTRACT: ?-Galactosylceramide (?-GalCer) is a typical antigen for invariant natural killer T cells that are a subset of T cells and play critical roles in regulating immune responses. To selectively induce the secretion of certain cytokines via introducing hydrogen-bonding interaction with polar amino acid residues in the binding pocket of CD1d, a series of ?-GalCer analogues with diether moiety in the acyl chain were designed and synthesized. The subsequent in vitro biological evaluation of these analogues revealed the structure-activity relationship for the selective IL-17 secretion. Analogues 5 and 6 induced the significantly increased IL-17 secretion over other cytokines, suggesting protective effects against pathogens. In contrast, analogue 7 showed the highly reduced IL-17 secretion, which may indicate potential anti-inflammatory effects.

SUBMITTER: Hwang YS

PROVIDER: S-EPMC6511956 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Improved Th17 Selectivity of α-Galactosylceramide via Noncovalent Interactions with Diether Moiety.

Hwang Yoon Soo YS Yim Junhyeong J Song Heebum H Park Seung Bum SB

ACS medicinal chemistry letters 20190404 5

α-Galactosylceramide (α-GalCer) is a typical antigen for invariant natural killer T cells that are a subset of T cells and play critical roles in regulating immune responses. To selectively induce the secretion of certain cytokines via introducing hydrogen-bonding interaction with polar amino acid residues in the binding pocket of CD1d, a series of α-GalCer analogues with diether moiety in the acyl chain were designed and synthesized. The subsequent <i>in vitro</i> biological evaluation of these ...[more]

PMID: 31097989

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