Artificial Glycosidase with Controlled Selectivity

具有受控选择性的人工糖苷酶

• 批准号: 10024717
• 负责人: Yan Zhao
• 金额: $ 29.91万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10024717
• 关键词: 3-Dimensional; Acidity; Active Sites; Affinity; Binding; Binding Sites; Biological; Biological Assay; Biological Process; Biology; Biomimetics; Buffers; Carbohydrates; Catalysis; Chemicals; Chemistry; Complement; Complex; Development; Endoglycosidases; Enzymes; Exoglycosidases; Generations; Genomics; Glycoside Hydrolases; Glycosides; Heterogeneity; Hydrolysis; Knowledge; Lectin; Length; Methods; Modification; Molecular; Oligosaccharides; Organic Synthesis; Oxygen; Peptides; Planet Earth; Polysaccharides; Positioning Attribute; Preparation; Proteins; Proteomics; Reporting; Research Design; Shapes; Site; Structure; Techniques; Technology; Time; Water; adduct; base; biological systems; catalyst; design; functional group; human disease; imprint; improved; insight; molecular recognition; molecular size; monomer; nanoparticle; public health relevance; receptor; reconstruction; small molecule; success; sugar; surfactant; three dimensional structure; tool

Artificial Glycosidase with Controlled Selectivity Abstract Carbohydrates are the most abundant biomolecules on the earth, and involved in numerous biological processes and all major human diseases. Glycoscience, nonetheless, lags behind genomics and proteomics, due to the extreme complexity, dynamic structural diversity, and micro-heterogeneity of glycans found in biological systems. Another reason, according to the 2012 NRC report “Transforming Glycoscience”, was the lack of suitable tools and methods “to detect, describe, and fully purify glycans…and then to characterize their chemical composition and structure. Molecular recognition of carbohydrates and peptides has been long-standing challenges in bioorganic and supramolecular chemistry, due to the importance of these molecules in biology. The PI’s group has developed protein-sized molecularly imprinted nanoparticles (MINPs) to bind a wide range of biologically interesting guests including carbohydrates and peptides. They are prepared and purified in < 2 days without any special techniques, once the template, functional monomers, and cross-linkable surfactants are available. MINP-based “synthetic lectins” were shown to recognize a wide range of mono- and oligosaccharides in water with tens of micromolar binding affinities. Oligosaccharides were distinguished based on their building blocks, glycosidic linkages, and chain length. The overall objective of this proposal is to develop synthetic glycosidases with selectivities unavailable in their natural counterparts. The proposed catalysts contain substrate-specific active sites with precisely installed catalytic groups for optimal catalysis. In the traditional synthesis of receptors and supramolecular catalysts, tremendous synthetic efforts are needed just to have a binding pocket. Fine tuning of the pocket for specific and complex biomolecules is nearly impossible. The micellar imprinting technology used in the MINP preparation, on the other hand, can quickly construct multifunctionalized, complex- shaped active sites from simple building blocks. The principles to be demonstrated are not limited to glycan hydrolysis and are expected to open up many possibilities in the design and synthesis of enzyme-mimicking catalysts.

具有控制选择性的人工糖苷酶 抽象的 碳水化合物是地球上最丰富的生物分子，参与 许多生物过程和所有主要人类疾病。但是，糖科学，尽管如此 由于极端的复杂性，动态结构，基因组学和蛋白质组学背后的滞后 在生物系统中发现的聚糖的多样性和微生物性。另一个原因， 根据2012年NRC报告“转化性糖科”，缺乏合适的 工具和方法“检测，描述和完全净化聚糖……然后表征 它们的化学成分和结构。 分子识别碳水合物和肽已经是长期存在的 由于这些的重要性，生物有机和超分子化学的挑战 生物学分子。 PI组已开发出蛋白质大小的分子印记 纳米颗粒（MINPS）结合了各种各样的生物学有趣的客人 碳水化合物和宠物。他们在<2天内准备和净化，没有任何特殊 一旦模板，功能单体和交叉连接表面活性剂为 可用的。显示基于MINP的“合成凝集素”可以识别多种单声道 和具有数十个微摩尔结合亲和力的水中的寡糖。寡糖 根据其基础，糖苷连接和链长度进行区分。 该提案的总体目的是开发与 他们的自然对应物中不可用的选择性。提出的催化剂包含 具有精确安装的催化基团的底物特异性活性位点可用于最佳催化。 在传统的受体和超分子催化剂的合成中，巨大的合成 只需要有一个装订的口袋就需要努力。对口袋进行微调，以适合特定和 复杂的生物分子几乎是不可能的。胶束烙印技术 另一方面，MINP的准备可以迅速构建多官能化的，复杂的 来自简单构建块的形状主动站点。要证明的原则不是 仅限于聚糖水解，并有望在设计中开放许多可能性 并合成模拟酶的催化剂。