Versatile Route to Synthesize Heterobifunctional Poly(ethylene glycol) of Variable Functionality for Subsequent Pegylation 英文参考文献.docVIP

Polymers 2012, 4, 561-589; doi:10.3390/polym4010561 OPEN ACCESS polymers ISSN 2073-4360 /journal/polymers Article Versatile Route to Synthesize Heterobifunctional Poly(ethylene glycol) of Variable Functionality for Subsequent Pegylation Redouan Mahou and Christine Wandrey * Institut d’Ingénierie Biologique et Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne, EPFL-SV-IBI-LMRP, Station 15, Lausanne CH-1015, Switzerland * Author to whom correspondence should be addressed; E-Mail: christine.wandrey@epfl.ch; Tel.: +41-21-693-96-61; Fax: +41-21-693-96-85. Received: 3 November 2011; in revised form: 31 January 2012 / Accepted: 8 February 2012 / Published: 16 February 2012 Abstract: Pegylation using heterotelechelic poly(ethylene glycol) (PEG) offers many possibilities to create high-performance molecules and materials. A versatile route is proposed to synthesize heterobifunctional PEG containing diverse combinations of azide, amine, thioacetate, thiol, pyridyl disul?de, as well as activated hydroxyl end groups. Asymmetric activation of one hydroxyl end group enables the heterobifunctionalization while applying selective monotosylation of linear, symmetrical PEG as a key step. The azide function is introduced by reacting monotosyl PEG with sodium azide. A thiol end group is obtained by reaction with sodium hydrosulfide. The activation of the hydroxyl end group and subsequent reaction with potassium carbonate/thioacetic acid yields a thioacetate end group. The hydrolysis of the thioester end group by ammonia in presence of 2,2′-dipyridyl disulfide provides PEG pyridyl disul?de. Amine terminated PEG is prepared either by reduction of the azide or by nucleophilic substitution of mesylate terminated PEG using ammonia. In all cases, 95% functionalization of the PEG end groups is achieved. The PEG derivatives particularly support the development of ma