O-glycosylation is one type of important protein modification and plays crucial roles in many cellular processes. Currently, there is limited commercial source for the glycosyl amino acid building blocks that can be utilized in glycopeptide synthesis. In this Phase I project, Life BioScience Inc. (LBSI) proposed to utilize its established glycan technologies and extensive research experience of its employees in carbohydrate chemistry to synthesize a chemical library of 36 O-linked core structures on amino acids (Ser/Thr) that have been protected by Fmoc for further glycopepetide synthesis. The proposed glycan compounds will be well purified (>98% purity) and structurally identified by NMR and Mass Spectrometry. New carbohydrate and peptide synthesis strategies including microwave-assisted synthesis, formation of alpha-O-GaINAc conformation, and [2+1] synthetic approach, will be empolyed in the sythetic routes leading to O-glycosyl amino acid building blocks. In addition, LBSI will collaborate with Dr. David Live at CCRC in Phase I to assemble the glycosyl building blocks to glycopeptides for proof-of-concept demonstration. At the end of the Phase I project, LBSI will provie the purified glycan samples to a NIGMS-designated screen center for the use as analytical standards in structural studies and carbohydrate-based high throughput assays.
