Versatile Route to Synthesize Heterobifunctional Poly(ethylene glycol) of Variable Functionality for Subsequent Pegylation

Polymers

Redouan Mahou¹ 

[1] id="af1-polymers-04-00561">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, Switzerla

关键词: heterobifunctional PEG;    pegylation;    selective monotosylation;    hybrid hydrogel;    cell microencapsulation;   

DOI  :  10.3390/polym4010561

来源: mdpi

【 摘 要 】

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 disulfide, 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 disulfide. 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 materials for biomedical applications. For example, grafting up to 13% of the Na-alg monomer units with α-amine-ω-thiol PEG maintains the gelling capacity in presence of calcium ions but simultaneous, spontaneous disulfide bond formation reinforces the initial physical hydrogel.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.