Applied Chemistry Department, National Yang Ming Chiao Tung University, No. 1001, University Road, Hsinchu City, 30010, Taiwan (China.
Institute of Biological Chemistry, Academia Sinica, No. 128, Academia Road Section 2, Nan-Kang, 11529, Taiwan (China.
ChemMedChem. 2023 Nov 16;18(22):e202300399. doi: 10.1002/cmdc.202300399. Epub 2023 Oct 20.
Mycobacterium tuberculosis (Mtb) causes tuberculosis as one major threat to human health, which has been deteriorated owing to the emerging multidrug resistance. Mtb contains a complex lipophilic cell wall structure that is important for bacterial persistence. Among the lipid components, sulfoglycolipids (SGLs), known to induce immune cell responses, are composed of a trehalose core attached with a conserved sulfate group and 1-4 fatty acyl chains in an asymmetric pattern. At least one of these acyl chains is polymethylated with 3-12 methyl branches. Although Mtb SGL can be isolated from bacterial culture, resulting SGL is still a homologous mixture, impeding accurate research studies. This up-to-date review covers the chemical synthesis and immunological studies of Mtb SGLs and structural analogues, with an emphasis on the development of new glycosylation methods and the asymmetric synthesis of polymethylated scaffolds. Both are critical to advance further research on biological functions of these complicated SGLs.
结核分枝杆菌（Mtb）是导致结核病的主要病原体之一，对人类健康构成严重威胁，而其日益严重的耐药性问题更是雪上加霜。Mtb 含有复杂的亲脂细胞壁结构，对于细菌的存活至关重要。在脂质成分中，硫苷脂（SGL）是已知能够诱导免疫细胞反应的物质，由海藻糖核心与保守的硫酸基团以及以不对称模式连接的 1-4 个脂肪酸链组成。这些酰基链中至少有一个被 3-12 个甲基支链多甲基化。尽管 Mtb SGL 可以从细菌培养物中分离出来，但得到的 SGL 仍然是同源混合物，阻碍了准确的研究。这篇最新综述涵盖了 Mtb SGL 及其结构类似物的化学合成和免疫学研究，重点介绍了新糖基化方法的发展和多甲基化支架的不对称合成，这两者对于深入研究这些复杂 SGL 的生物学功能至关重要。
