SBIR PHASE I. TOPIC321:CHEMICALLY DEFINED GLYCAN LIBRARIES FOR REFERENCE STANDARD

鞘糖脂是人体质膜的重要组成部分。超过300人 已对鞘糖脂多糖进行了表征。葡聚糖直接参与了分子 表彰活动。许多与癌症相关的鞘糖脂多糖正在被开发为 癌症疫苗。大多数鞘糖脂多糖都不能在市场上买到。对于一个有限的 商业上可用的数量非常高。我们已经开发出了高效的一锅锅 多酶(OPME)方法用于高产量和高成本效益的复合多糖生产。这个 OPME方法将用于建立一个由60种结构多样的神经鞘糖脂糖链组成的文库 包括那些含有不同天然唾液酸形式的唾液酸。三个具体目标是 合成1)神经节系列；2)乳糖和新乳糖系列；以及3)球状和等球状系列 使用我们已建立的高效OPME策略的鞘糖脂多糖。60个人中的每一个 化合物将在GLP条件下合成，规模为10-50 mg，提纯到&gt；98%的纯度，以及 用核磁共振波谱和高分辨质量表征 光谱分析(HRMS)。对于所有合成的多糖(&gt；98%纯度L 50微克)，将被发送到 NIGMS设计的用于验证测试、多糖微阵列和其他筛选的筛选中心 化验。这些多糖是生物检测和生物医学中必不可少的标准和无价的探针。 申请。

Glycosphingolipids are essential components of human plasma membrane. More than 300 glycosphingolipid glycans have been characterized. The glycans are directly involved in molecular recognition event. A number of cancer-associated glycosphingolipid glycans are being developed as cancer vaccines. Most glycosphingolipid glycans are not commercially available. The costs for a limited number of commercially available ones are extremely high. We have developed highly effective one-pot multienzyme (OPME) approaches for high-yield and cost-effective production of complex glycans. The OPME approaches will be used in generating a library of 60 structurally diverse glycosphingolipid glycans including those contain different naturally occurring sialic acid forms. Three specific aims are to synthesize 1) ganglio-series; 2) lacto- and neolacto-series; and 3) globo- and isoglobo-series glycosphingolipid glycans using our established high efficient OPME strategies. Each of the 60 compounds will be synthesized under GLP conditions in 10-50 mg scale, purified to >98% purity, and characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). For all glycans synthesized (>98% purityL 50 micrograms of each will be sent to an NIGMS-designed screening center for validation testing, glycan microarray and other screening assays. These glycans are essential standards and invaluable probes for bioassays and biomedical applications.