SYNTHESIS AND PHYSICOCHEMICAL PROPERTIES OF PROTEIN CONJUGATES WITH WATER-SOLUBLE POLY(ALKYLENE OXIDES)

Conjugates of proteins (bovine serum albumin (BSA) and alpha-chymotryp sin (CHT)) with poly(ethylene glycol) and amphiphilic block copolymers of ethylene oxide and propylene oxide (proxanols) were synthesized, u sing monoaldehyde polymer derivatives as the amino group modifying rea gents. Four types of conjugates varying in the placement of hydrophobi c block and type of polymer chain distribution were obtained. Methods of purification and characterization of proteins conjugated with proxa nols were developed. It was shown that conjugates based on CHT retain high enzymatic activity toward both substrates investigated-N-benzoyl- L-tyrosine and casein-up to high degrees of modification (11 polymer c hains per protein molecule). At the same time, CHT-proxanol conjugates were characterized by higher thermostability, the stabilizing effect increasing in parallel with the degree of modification. It was shown t hat the alteration of sedimentation coefficients of proteins caused by modification was negligible. On the basis of data obtained by the met hods of hydrophobic chromatography, sedimentation, and differential sc anning calorimetry, conformational models of protein-proxanol conjugat es were suggested. It was supposed that conjugates form compact struct ures in aqueous solutions, which resemble intramolecular micelles, sta bilized by hydrophobic interactions between poly(propylene oxide) bloc ks of proxanols.