Vous êtes sur la page 1sur 1

Construction of Biological Function Carbohydrate Mimetics and Novel Sugar Aminoxy Acid Building Blocks Derivatives-Medical journal A great

deal of attention has been focused on glycochemistry due to its signifance and alarming interests by researchers in the studies of drug discoveries. The sugar chemistry branches have been extended to a wide range of research fields incuding organic chemistry, biological chemistry, material and medicinal chemistry based on their structure diversities. According to the development and significance of carbohydrate chemistry, the thesis elaborates on glycomics, sugar-based drug development and functional carbohydrate mimetics respectively. Glycoscience promotes the achievements in biology, medicine, immunology, and as well as the progress of human science. On the basis of these inter-disciplinary subjects, our studies in this thesis paper toward glycoscience could be divided into two parts:Part 1Protein tyrosine phosphatases 1 Beta (PTP1B) are important regulators of signal transduction pathways. Potent and selective PTP1B inhibitors are useful for probing these pathways and also may serve as drugs for the treatment of a variety of diseases including type 2 diabets, obesity and breast cancer. In the first Part, we use Cu (I)-catalyzedClick cycloaddition reactions between azides and alkynes to generate PTP1B inhibitors of triazole-linked glycosyl amino acid, acetophenone, benzoic acid and a-ketocarboxylic acid derivatives. Among the synthesized glycoconjugates, the triazolyl a-ketocarboxylic acids were identified as the most potent PTP1B inhibitors.35,36,38 and 40 had an IC50 value of 1.5,4.8,3.2,5.6M against PTP1B respectively. Interestingly, bidentate pyranoglucosides bearing two triazolyl a-ketoester groups on the 2,6-or 3,4-positions of sugar scaffold 35 and 36 displayed unexpected selective fluorescence quenching in the presence of Ni2+Part 2The rapidly growing importance of carbohydrates in biological systems and their potential medical applications incite the synthesis of various carbohydrate mimetics. In the second Part, we synthesized sugar aminoxy acids a new class of sugar building blocks containing both aminoxy and carboxylic acid functional groups on the sugar ring. Aminoxy and carboxylic acid functional groups might be introduced into the different positions of pyranosyl sugar rings. We prepared 6-O-amino-2-O-carboxymethyl glucopyranosides as building block to construct oligosaccharide mimetics of dimer, trimer and tetramer successfully. The conformations of the dimer, trimer and tetramer were probed by using CD spectroscopic methods. In our continuing program on the development of carbohydrate mimetics, we study on the synthesis of 4-O-amino-3-O-carboxymethyl glucopyranosides. These molecules could be readily used for the synthesis of various glycoconjugates through amide bond, thus providing a potent tool for the preparation of novel functional carbohydrate mimetics. Reference: Medical information: http://www.nlm.nih.gov/medlineplus/ medical questions answered: http://www.healthqas.org health news: http://www.medicalnewstoday.com