Novel reactive PEG for amino group conjugation

Abstract

Activated mPEG carbonates are important reagents that have been widely used for the PEGylation of several peptides and proteins by means of stable urethane linkages. In fact, mPEG-N-hydroxysuccinimidyl carbonate and mPEG-p-nitrophenyl carbonate are among the most used reagents in PEGylation technology. However, the synthesis and storage of these reagents are not always easy to resolve. With the aim of surpassing some of the drawbacks associated with the use of activated mPEG-carbonates we have prepared and evaluated a new mPEG-carbonylimidazolium iodide, which can be used for the conjugation of the NH₂ group by means of urethane linkages, as an interesting alternative to the known reagents. It is noteworthy that the novel reagent is prepared by a simple two-step procedure under mild experimental conditions. Moreover, we performed a detailed study of the conjugation reaction of interferon-α2b with the carbonylimidazolium derivative, and evaluated the conjugate in in vitro and in vivo studies.