PEGylation by Urethane Linkage Formation

Reagent 8 has been used in the PEGylation of ribonuclease and superoxide dis-mutase [39], doxorubicin [44], recombinant mammalian urate oxidase [45], uricase [46] and lysozyme [47]. However, it has been reported that PEGylations with reagent 8 leave lipophilic toxic impurities on the conjugated material and thus the use of this derivative is now limited. 

5-trichlorophenylchloroformate [39]. Although important in early studies, the use of this reagent has almost been abandoned in recent developments. 

Activated polymer 11 is a mild PEGylating reagent that has been applied in pioneering conjugations of different proteins such as superoxide dismutase [52], a2-macro-globulin [55], lactoferrin [52], streptokinase [55], alkaline phosphatase [56], IgG [57] and urokinase [58]. 

Related to 11, Valllard and coworkers have recently prepared the more reactive alkoxy-carbonyl imidazolium iodide 12 and successfully used this reagent for the PEGylation of IFN a-2b [59]. Of note, reagent 12, which can easily be prepared by alkyation of 11 under mild reaction conditions, affords excellent yields of conjugation even at short reaction times. 

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Handbook of Polymers for Pharmaceutical Technologies 3.3.1 PEGylation by Urethane Linkage Formation... 

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