Li Zhihao, Bavaro Teodora, Tengattini Sara, Bernardini Roberta, Mattei Maurizio, Annunziata Francesca, Cole Richard B, Zheng Changping, Sollogoub Matthieu, Tamborini Lucia, Terreni Marco, Zhang Yongmin
Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 Place Jussieu, 75005, Paris, France.
Drug Sciences Department, University of Pavia, Viale Taramelli 12, 27100, Pavia, Italy.
Eur J Med Chem. 2020 Oct 15;204:112578. doi: 10.1016/j.ejmech.2020.112578. Epub 2020 Jul 15.
Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB.
导致结核病（TB）的分枝杆菌感染是2018年全球十大主要死因之一，而脂阿拉伯甘露聚糖（LAM）已被确认为结核杆菌细胞表面最重要的抗原性多糖。在本研究中，已开发出一种简便的合成方法来合成三种源自LAM的支链寡糖，其中通过流动化学中的酶促水解制备核心构建块，产率优异。经过几步糖基化反应后，将所得寡糖与重组人血清白蛋白（rHSA）偶联，并使用从几名结核病感染患者获得的血清进行体外ELISA试验，以评估糖缀合物产品对人LAM抗体的亲和力。评估结果为阳性，尤其是化合物21表现出优异的活性，可被视为未来开发新型抗结核糖缀合物疫苗的先导化合物。
