Synthetic Study on Semi-synthetic Antibody

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14979
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: OTAKA Akira 徳島大学, 大学院医歯薬学研究部(薬学系), 教授 (20201973)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: ペプチド / 蛋白質 / チオエステル / アシル基転移反応

Outline of Final Research Achievements

In this study, chemical methodology for the conversion of naturally occurring peptide sequences to the thioester units or their equivalent. We developed two innovative methodologies for this purpose. One methods uses the Ni(II)-coordination to four residue sequence, consisting of Ser-Xaa-His-Yaa. After coordination of the Ni(II) to the four residue sequence, four sequential acyl-transfer occurred to produce peptide hydrazide. The resulting hydrazide could be successfully converted to the corresponding thioesters. Other procedure utilizes the regioselective S-cyanylation followed by hydrazynolysis of the N-terminal side peptide bond of the cyanylation residue. This procedure allowed for the formation of thioester. Established two methodologies were successfully applied to the conversion of various type of naturally occurring peptide sequences to the corresponding peptide and protein thioesters. And such thioesters will find great utility for the semi-synthesis of antibody molecules.

Free Research Field

創薬化学