Site-specific N-terminus conjugation of poly(mPEG1100) methacrylates to salmon calcitonin: synthesis and preliminary biological evaluation

Abstract

Recent advances in polymerization strategies have led to the development of novel polymer–(poly)peptide biohybrid materials with potential application in the field of macromolecular therapeutics. In this current work, comb-shaped α-aldehyde poly(monomethoxy polyethylene glycol)methacrylates (p(mPEG)MA) with molecular masses in the 6.5–109 kDa range were prepared and conjugated, via reductive amination, to the Cys1N-terminus of salmon calcitonin (sCT), a calcitropic hormone currently administered for the treatment of a number of hypercalcaemia-related diseases. The conjugation site was determined by tryptic digestion of the sCT–p(mPEG1100)MA biohybrids in conjunction with LC-MS MALDI-TOF spectrometry. Preliminary in vitro biological tests show that the polymer conjugation does not interfere with the biological activity of the sCT.