Synthetic Studies of Bacterial Glycans

细菌表面覆盖着碳水化合物分子（聚糖），这些分子在细菌的生命周期中起着至关重要的作用。这些聚糖通常是生命所必需的，有助于保护这些生物体免受环境的侵害，经常调节受感染宿主的免疫系统。这些碳水化合物组装的途径是药物作用的潜在靶点，基于这些结构的疫苗是有效的抗感染保护剂。化学合成用于基础化学和生化研究的细菌聚糖的能力是实现这些更医学相关目标的必要先决条件。几年来，我的小组一直在研究分枝杆菌中聚糖的合成、构象和生物化学，包括结核分枝杆菌，这种引起结核病的有机体。最近，我们开始了一个从空肠弯曲杆菌中提取聚糖的合成项目，这是一种常见的食物中毒原因。

The surfaces of bacteria are coated with carbohydrate-containing molecules (glycans) that play critical roles in their life cycles. These glycans are usually essential for life and help protect these organisms from their environment, often modulating the immune system of infected hosts. The pathways by which these carbohy- drates are assembled are potential targets for drug action, and vaccines based on these structures are effective protectants against infection. The ability to chemically synthesize bacterial glycans for use in fundamental chemical and biochemical studies is a necessary prerequisite to achieving these more medically relevant goals. My group has, for several years, studied the synthesis, conformation and biochemistry of glycans from mycobacteria, including Mycobacterium tuberculosis, the organism that causes tuberculosis. Recently, we began a synthetic program on glycans from Campylobacter jejuni, a common cause of food poisoning. We propose here to continue our program on the synthesis of bacterial glycans by focusing on three areas. We will: 1) Expand our synthetic work on campylobacter glycans; 2) Synthesize structurally defined polysaccharides as probes for lipopolysaccharide biosynthesis; 3) Synthesize bradyrhizose, a bicyclic monosaccharide found in rhizobia, and related derivatives. A critical component in all of these projects is the need to develop new synthetic approaches and methodology to address either the unusual structure of the targets or the size of the molecules. Of particular significance, the targets have received little attention from synthetic chemists to date. Our work will be the first in this area and will thus be influential to others working in the field, much like our previous studies of mycobacterial glycan synthesis. This program will provide state-of-the-art training in complex glycan synthesis supported by a program dedicated to the development of independent scientists with a knowledge entrepreneurship and intellectual property. The synthetic work proposed here will lead to molecules for use in studies by collaborators directed at understanding, in greater detail, the assembly and biological role of bacterial glycans.