Novel ionic-based tools for glycoscience

细胞表面碳水化合物作为分子指纹提供了巨大的未开发潜力，可以区分疾病细胞和正常细胞。然而，细胞表面的葡聚糖在表征分子方面具有极大的挑战性，需要在高度专业化的技术和专业知识上进行重大投资，这正是它们的全部潜力尚未实现的原因。开发使细胞表面碳水化合物研究成为可能的工具，为开发早期诊断测试以及新的治疗靶点和疫苗提供了可能性。尽管这些复杂分子很重要，但合成结构确定的复杂碳水化合物仍然是一个非常费力的过程，需要高水平的技术专业知识。缺乏快速、高通量的合成方法来提供纯产品阻碍了糖生物学研究的进展，糖生物学研究不得不依赖孤立的材料或传统的、冗长的、靶向的寡糖合成。这是一个涉及合成有机化学家、糖生物学家、酶学家和分子生物学家的多学科项目。该提案的核心是遵循我们团队最近开发的方法学，以化学和酶法合成新型O-葡聚糖工具，由此将采用一种基于多功能离子标签的“捕捉并释放”策略，该策略不需要在每个反应步骤后进行层析，并且与化学和酶法低聚糖合成方案兼容。这种新型的寡糖探针将用于研究与疾病相关的胃肠道和眼部粘蛋白的O-糖基化模式。我们正在解决一个及时的问题--缺乏可供研究的O-葡聚糖探针--同时开发合成工具，使主流化学家能够合成低聚糖。

Cell surface carbohydrates offer tremendous unexploited potential as molecular fingerprints that can distinguish disease cells from normal cells. However, cell-surface glycans are extraordinarily challenging molecules to characterize, requiring major investments in highly specialized technology and expertise and that is precisely why their full potential has not yet been realized. Developing the tools that will make the study of cell surface carbohydrates possible, offers the possibility of developing early diagnostic tests, as well as new therapeutic targets and vaccines. Despite the importance of these complex molecules, the synthesis of structurally defined complex carbohydrates is still a very laborious process that requires a high level of technical expertise. This lack of rapid, high throughput synthetic methodologies to provide pure products has hampered progress in glycobiology research, which has had to rely on either isolated materials or traditional, lengthy, target-oriented oligosaccharide synthesis. This is a multidisciplinary project involving synthetic organic chemists, glycobiologists, enzymologists and molecular biologists. The proposal centers on the chemical and enzymatic synthesis of novel O-glycan tools following the methodology recently developed within our team, whereby a versatile ionic tag based "catch-and-release" strategy that requires no chromatography after each reaction step, and that is compatible with chemical and enzymatic oligosaccharide synthetic protocols will be employed. The novel oligosaccharide probes will be used for the study of the O-glycosylation patterns of gastrointestinal and ocular mucins that are relevant to disease. We are addressing a timely problem - lack of O-glycan probes for study - while developing the synthetic tools to make oligosaccharide synthesis available to main stream chemists.