Anchimeric assistance effect on regioselective hydrolysis of branched PEGs: a mechanistic investigation

详细信息    查看全文

• 作者：Guiotto ; Andrea ; Canevari ; Mirta ; Pozzobon ; Michela ; Moro ; Stefano ; Orsolini ; Piero ; Veronese ; Francesco M.
• 关键词：Poly(ethylene glycol) ; Branched PEG ; Hydrolysis
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2004
• 出版时间：October 1, 2004
• 年：2004
• 卷：12
• 期：19
• 页码：5031-5037
• 全文大小：342 K

文摘

Branched poly(ethylene glycols) (PEG2) are nowadays widely used for protein and peptides bioconjugation, for their favourable properties (such as the ability to protect the protein surface in an aaaumbrella likeaaa fashion). The discovery that mPEG₂-LysMetaa AlaOEt lost one mPEG chain during standard base-catalysed ester hydrolysis conditions prompted us to investigate the hydrolytic stability of such systems and the mechanism involved in the PEG chain loss. A series of branched PEGs, substituted with different aminoacids and dipeptides, have been prepared to test the influence of steric hindrance, chain lengths, ramification and Lys-AA amide substitution on hydrolysis. Unexpected results reveal an anchimeric assistance of the Lys-AaA amide proton to the hydrolysis of the carbamoyl moiety joining mPEG to the aa-amino group of lysine through the formation of an hydantoin system.