The synthesis and characterization of an active poly(ethylene glycol) (PEG) derivative with new properties has been afforded starting from a side reaction of N-hydroxysuccinimide (NHS) in presence of N,N-dicyclohexylcarbodiimide (DCC). In particular, a ring opening of NHS in presence of DCC forms a β-alanine active derivative, through Lossen rearrangement, which then reacts with PEG-NH2 yielding the active PEG derivative: PEG-NH-CO-βAla-NH-CO-NHS. The active group R–NH-CO-NHS showed lower reactivity towards amines and a higher stability in alkaline solution. This can be especially useful in polymer coupling to proteins, because it may lead to a better selectivity among all the amino groups present in a protein, thus yielding less heterogeneous PEG-protein conjugates mixture because only the most nucleophilic and solvent exposed amines can react. A comparison with one of the most used PEGylating agent, the PEG-succinimidyl carboxymethylate (PEG-O-CH2-CO-NHS), displayed the usefulness of this new PEG derivative for obtaining PEG-protein conjugates. Furthermore, it is of interest that the obtained protein-conjugates are slowly hydrolyzed in water releasing the free protein, therefore they can be considered protein prodrugs.

New active poly(ethylene glycol) derivative for amino coupling

PASUT, GIANFRANCO;SCHIAVON, ODDONE;VERONESE, FRANCESCO
2007

Abstract

The synthesis and characterization of an active poly(ethylene glycol) (PEG) derivative with new properties has been afforded starting from a side reaction of N-hydroxysuccinimide (NHS) in presence of N,N-dicyclohexylcarbodiimide (DCC). In particular, a ring opening of NHS in presence of DCC forms a β-alanine active derivative, through Lossen rearrangement, which then reacts with PEG-NH2 yielding the active PEG derivative: PEG-NH-CO-βAla-NH-CO-NHS. The active group R–NH-CO-NHS showed lower reactivity towards amines and a higher stability in alkaline solution. This can be especially useful in polymer coupling to proteins, because it may lead to a better selectivity among all the amino groups present in a protein, thus yielding less heterogeneous PEG-protein conjugates mixture because only the most nucleophilic and solvent exposed amines can react. A comparison with one of the most used PEGylating agent, the PEG-succinimidyl carboxymethylate (PEG-O-CH2-CO-NHS), displayed the usefulness of this new PEG derivative for obtaining PEG-protein conjugates. Furthermore, it is of interest that the obtained protein-conjugates are slowly hydrolyzed in water releasing the free protein, therefore they can be considered protein prodrugs.
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/2452572
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 25
social impact