Anchimeric assistance effect on regioselective hydrolysis of branched PEGs: a mechanistic investigation
| Autor: | Mirta Canevari, Stefano Moro, Francesco M. Veronese, Andrea Guiotto, Piero Orsolini, Michela Pozzobon |
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| Rok vydání: | 2004 |
| Předmět: |
Steric effects
Bioconjugation Stereochemistry Hydrolysis Lysine Organic Chemistry Clinical Biochemistry Pharmaceutical Science Regioselectivity Hydantoin Dipeptides Alkaline hydrolysis (body disposal) Biochemistry Polyethylene Glycols chemistry.chemical_compound chemistry Drug Stability Amide Drug Discovery Molecular Medicine Moiety Amino Acids Molecular Biology |
| Zdroj: | Bioorganicmedicinal chemistry. 12(19) |
| ISSN: | 0968-0896 |
| Popis: | 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 'umbrella like' fashion). The discovery that mPEG(2)-LysMetbeta 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 alpha-amino group of lysine through the formation of an hydantoin system. |
| Databáze: | OpenAIRE |
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