α-硫酸脑苷脂类似物的合成及其对人T细胞刺激活性的评估

Synthesis and evaluation of human T cell stimulating activity of an alpha-sulfatide analogue.

作者信息

Franchini Laura, Matto Pamela, Ronchetti Fiamma, Panza Luigi, Barbieri Lucia, Costantino Valeria, Mangoni Alfonso, Cavallari Marco, Mori Lucia, De Libero Gennaro

机构信息

Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano, Via Saldini 50, 20133 Milano, Italy.

出版信息

Bioorg Med Chem. 2007 Aug 15;15(16):5529-36. doi: 10.1016/j.bmc.2007.05.044. Epub 2007 May 23.

DOI:10.1016/j.bmc.2007.05.044

PMID:17544671

Abstract

A concise synthesis of alpha-sulfatide 1, an analogue of natural glycolipid antigens with potential anti-tumor activity, was performed. Two different approaches to the alpha-glycosidic bond were explored, resulting in a high yield and excellent stereoselectivity. Compound 1 combines the structural features of sulfated beta-GalCer (sulfatide) and alpha-GalCer, which activate specific T cells. alpha-Sulfatide 1 was stimulatory for CD1d-restricted semi-invariant Natural Killer T (iNKT) cell clones, although less potent than alpha-GalCer, while it was not recognized by CD1a-restricted sulfatide-specific T cells.

摘要

完成了具有潜在抗肿瘤活性的天然糖脂抗原类似物α-硫酸脑苷脂1的简洁合成。探索了两种不同的形成α-糖苷键的方法，获得了高产率和优异的立体选择性。化合物1结合了硫酸化β-半乳糖神经酰胺（硫酸脑苷脂）和α-半乳糖神经酰胺的结构特征，二者均可激活特定的T细胞。α-硫酸脑苷脂1对CD1d限制性半不变自然杀伤T（iNKT）细胞克隆具有刺激作用，尽管效力低于α-半乳糖神经酰胺，而它不被CD1a限制性硫酸脑苷脂特异性T细胞识别。