Studies Of Site Specific Incorporation Of Thioamide Linkages Into Bioactive Peptides

Bioactive peptides because of its physiological activity such as anti-tumor, anti-fungal, antiviral and immunomodulatory are of great concern in the field of drug research. However, peptide drugs show poor stability in vivo, degradation is primarily due to amide bond cleavage by proteolytic enzymes. Therefore, considerable effort has been undertaken to discover analogues with greater resistance to degradation. The incorporation of thioamide bonds might provide a promising approach for the preparation of pharmacologically important peptides. We designed a model route for the site specific incorporation of thioamide linkages into a growing peptide by the thioacylation of peptides.Bioactive tetrapeptide acetyl-Asp-Gln-Tyr-GlyNH2is an endogenous growth-modifying peptide, existing in extracts of neuroblastoma tissue, in neuroblastoma cell cultures and in new-born pig brain tissue, it decreases in vitro growth of neuroblastoma cells. We would modify the structure of the tetrapeptide by the designed model route, complete the synthesis of the original tetrapeptide and3derivative thiopeptides, and detect the changes of biological activity.