Hwang Yoon Soo, Yim Junhyeong, Song Heebum, Park Seung Bum
CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University, Seoul 08826, Korea.
Department of Biophysics and Chemical Biology, Seoul National University, Seoul 08826, Korea.
ACS Med Chem Lett. 2019 Apr 4;10(5):720-725. doi: 10.1021/acsmedchemlett.8b00556. eCollection 2019 May 9.
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 biological evaluation of these analogues revealed the structure-activity relationship for the selective IL-17 secretion. Analogues and induced the significantly increased IL-17 secretion over other cytokines, suggesting protective effects against pathogens. In contrast, analogue showed the highly reduced IL-17 secretion, which may indicate potential anti-inflammatory effects.
α-半乳糖神经酰胺（α-GalCer）是不变自然杀伤T细胞的典型抗原，不变自然杀伤T细胞是T细胞的一个亚群，在调节免疫反应中起关键作用。为了通过与CD1d结合口袋中的极性氨基酸残基引入氢键相互作用来选择性诱导某些细胞因子的分泌，设计并合成了一系列在酰基链中带有二醚部分的α-GalCer类似物。随后对这些类似物的生物学评估揭示了选择性白细胞介素-17（IL-17）分泌的构效关系。类似物 和 诱导IL-17分泌比其他细胞因子显著增加，表明对病原体有保护作用。相比之下，类似物 显示IL-17分泌高度降低，这可能表明有潜在的抗炎作用。
