SBIR TOPIC321:CHEMICALLY DEFINED GLYCAN LIBRARIES FOR REFERENCE STANDARDS AND GLY

Cell-surface oligosaccharides appended to proteins and lipids are key binding epitopes in many critical biological processes, including bacterial infection, cell development and the immune response. Understanding these processes at the molecular level requires access to a wide range of oligosaccharides of known structure to support investigations of enzyme substrate binding and specificity, to screen for carbohydrate binding proteins, and to develop assays for enzymic activity. These oligosaccharides are currently unavailable in the commercial sector, thus impeding progress in this field. To address this deficiency, the proposed project focuses on the synthesis of oligosaccharides derived from the parent high-mannose oligosaccharide (14-mer) that is transferred en-bloc to polypeptides during translation. Twenty-eight (28) high-mannose oligosaccharides ranging in size from tri- to hexa-saccharides will be prepared. Chemical routes will be used to synthesize each oligosaccharide in 0.2 mg or greater quantities and in high purity, as determined by NMR, highresolution mass spectrometry, and high-pressure liquid chromatography. Samples of each oligosaccharide, along with pertinent analytical data, will be packaged and shipped to the NCI for use in theconstruction of glycan arrays to screen for carbohydrate binding proteins, and for other biochemical or biomedical applications. This Phase I project will develop robust synthetic protocols that will be used in subsequent Phase II studies where the chemical space will be extended beyond hexasaccharides. These latter syntheses will be difficult to conduct without the knowledge, experience and technical know-how gained from the proposed Phase I work. PUBLIC HEALTH RELEVANCE