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.

选择性可控的人工糖苷酶