Development of synthetic platoform of proteins

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390026
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: OTAKA Akira 徳島大学, ヘルスバイオサイエンス研究部, 教授 (20201973)
• Co-Investigator(Kenkyū-buntansha): SHIGENAGA Akira 徳島大学, 大学院ヘルスバイオサイエンス研究部, 講師 (10423394)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: タンパク質 / タンパク質化学合成 / チオエステル / Native Chemical Ligation

Outline of Final Research Achievements

We have developed N-sulfanylethylanilide (SEAlide) peptides. Extensive examination of SEAlide peptides showed that the amide-type SEAlide peptides can be directly and efficiently involved in NCL via thioester species in the presence of phosphate salts. The presence or absence of phosphate salts provided kinetically controllable chemoselectivity in NCL for SEAlide peptides. This allowed SEAlide peptides to be used in both one-pot/N-to-C-directed sequential NCL under kinetically controlled conditions, and the convergent coupling of large peptide fragments, which facilitated the chemical synthesis of proteins over about 100 residues. The use of SEAlide peptides, enabling sequential NCL operated under kinetically controlled conditions, and the convergent coupling, were used for the total chemical synthesis of a 162-residue monoglycosylated GM2-activator protein (GM2AP) analog.

Free Research Field

医薬品化学、ペプチド化学