Methodology for the Synthesis of Structurally Homogeneous N-Linked Glycopeptides

 描述（由申请人提供）：该项目涉及开发方法，提供方便的同质糖蛋白。具体而言，PI及其在西雅图大学（SU）的本科研究团队将开发一种新型、有效的N-连接糖肽从头合成方法，该方法采用通过酰肼糖基化生成的β-糖基酰肼作为β-葡糖胺替代物。 所提出的合成N-连接糖肽的方法将利用酰肼糖基化反应来提供具有天然糖苷键的糖肽，并且比传统方法具有更高的效率。目前的羟胺和酰肼糖基化方法产生具有含有肟、羟胺或肼聚糖-肽键的非天然N-连接糖蛋白的糖蛋白，因此目前的方法使得化学家和生物学家难以有信心地研究聚糖结构对蛋白质功能的影响。 PI选择在SU（一个主要的本科院校）从事他的独立职业，这样他的研究项目就可以同时影响科学界并改变本科生的生活。PI自2005年在SU开始职业生涯以来所做的所有研究都是与本科研究生合作完成的;本科生将与PI在这里提出的工作的各个方面并肩工作。

 DESCRIPTION (provided by applicant): This project involves the development of methodologies that provide convenient access to homogeneous glycoproteins. Specifically, the PI and his undergraduate research team at Seattle University (SU) will develop a novel, efficient de novo synthesis of N-linked glycopeptides that employs ß-glycosylhydrazides, generated via hydrazide glycosylation, as ß-glycosylamine surrogates. The proposed method to synthesize N-linked glycopeptides will harness hydrazide glycosylation reactions to provide glycopeptides with natural glycosidic linkages and with greater efficiency than traditional methods. Current oxyamine and hydrazide glycosylation methods produce glycoproteins with non-natural N-linked glycoproteins containing oxime, oxyamine, or hydrazine glycan-peptide linkages and thus current methods make it difficult for chemists and biologists to study with confidence the influence of glycan structure on protein function. The PI chose to pursue his independent career at SU, a predominantly undergraduate institution, so that his research program could simultaneously impact the scientific community and transform the lives of undergraduate students. All of the research the PI has performed since he began his career at SU in 2005 has been done in collaboration with undergraduate research students; undergraduate students will work side-by-side with the PI on all aspects of the work proposed here.