Newly Designed Amino Acids Glycopeptide Synthesis And Properity Research

PTP1B(Protein Tyrosine Phosphatase 1B) is a potential target for treating diabetes, obesity and some cancers, and thus it has been attached great importance in recent years. Triazolyl glycosyl amino acids synthesized via click chemistry and aryl C-glycosides have been found to display exciting PTPIB inhibitory efficacy in the previous work of our lab. In this paper, we expected to take advantage of the two natural-like products, and thereby designed and synthesized a series of compounds with the sugar as the skeleton, a 2, 4-dimethoxy phenyl introduced to the anomeric carbon, and a phenylalanine or a tyrosine introduced to the C-6 position. Also we gauged their inhibition activity in vitro. The results show that compound 18,19,20,21 are modest PTP1B inhibitors, and compound 20 has moderate selectivities over SHP-1, SHP-2 and TCPTP, which are also protein tyrosine phosphatases and share high sequence homology with PTP1B yet play distinct physiological roles.Peptides of aminoxy acids are oxa-analogues of peptides where an oxygen atom is introduced between the nitrogen atom of the amino and its adjacent carbon atom. They form more stable turn and helix structures than peptides, and are, therefore, of more pharmaceutical interest. In this work, we design a glycopeptide molecular of aminoxy acid, and expect to evaluate its potential biological activity. This molecule takes the serine as the building block, which is first modified to an aminoxy acid, and then converted to reacting blocks with the carboxyl and amino group bared respectively. These reacting blocks are combined with each other to yield the peptide of aminoxy acid through N-terminal acetylation and C-Terminal Amidation. The resulting peptide is then linked to the sugars to give the final product. In current, those partly protected aminoxy acids have already been successfully synthesized.