Synthetic Studies of Bacterial Glycans

细菌的表面覆盖着含碳水化合物的分子（聚糖），这些分子在细菌的生命周期中起着关键作用。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影响，通常调节受感染宿主的免疫系统。这些碳水化合物的组装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。化学合成细菌聚糖用于基础化学和生物化学研究的能力是实现这些医学相关目标的必要先决条件。我的小组已经研究了几年，从分枝杆菌，包括结核分枝杆菌，导致结核病的有机体的聚糖的合成，构象和生物化学。最近，我们开始了一项关于空肠弯曲杆菌聚糖的合成计划，空肠弯曲杆菌是食物中毒的常见原因。 我们建议在这里继续我们的计划，通过集中在三个领域的细菌聚糖的合成。我们将：1）扩大我们对弯曲杆菌聚糖的合成工作; 2）合成结构确定的多糖作为脂多糖生物合成的探针; 3）合成根瘤菌中发现的双环单糖--慢生根瘤糖及其相关衍生物。所有这些项目的一个关键组成部分是需要开发新的合成方法和方法，以解决目标的不寻常结构或分子的大小。特别重要的是，迄今为止，合成化学家很少关注这些目标。我们的工作将是这一领域的第一个，因此将对该领域的其他工作产生影响，就像我们以前对分枝杆菌聚糖合成的研究一样。该计划将提供复杂聚糖合成方面的最先进培训，并由一个致力于培养具有知识创业精神和知识产权的独立科学家的计划提供支持。这里提出的合成工作将导致分子用于合作者的研究，旨在更详细地了解细菌聚糖的组装和生物学作用。

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.