Development of simple synthetic method of glycoprotein besed on GlycoPEGylation

• Project/Area Number: 26860019
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical pharmacy
• Research Institution: The Noguchi Institute
• Principal Investigator: Goto Kohtaro 公益財団法人野口研究所, 研究部, 研究員 (30321673)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: PEG化 / 糖転移反応 / PEG / Endo-M / GlycoPEGylation / 糖加水分解酵素

Outline of Final Research Achievements

Conventional "GlycoPEGylation" is a synthetic method of glycoproteins attached PEG using glycosyltransferase. This strategy is very difficult to prepare a large amount of target compounds connected PEG owing to the use of glycosyltransferase. In order to resolve this problem, the development of "GlycoPEGylation" using a glycosylhydrolase represented by Endo-M was attempted.
A result of various studies, disaccharide oxazoline derivative which was consist of mannosyl-(β1-4)-N-acetyl glucosamine residues connected two PEG chains to 3’ and 6’ positions of the mannose residue was prepared and used as a glycosyl donor. Furthermore, subsequent enzymatic transglycosylation by using Endo-M was obtained a desired transglycosylated compound.