Covalent immobilization of biological molecules to maleic anhydride and methyl vinyl ether copolymers?A physico-chemical approach

Abstract

ABSTRACT:The covalent grafting of biological molecules to copolymers of maleic anhydride and methyl vinyl ether (MAMVE) has been used in various applications in diagnostics. To tentatively elucidate the phenomena involved in the control of the immobilization of oligodeoxynucleotides and proteins, the physico-chemical properties of MAMVE copolymers were investigated. Because the grafting mixture contains water, to allow dissolution of the biomolecules without loss of biological properties, the anhydride-based copolymer evolves from a neutral to a negatively charged macromolecule due to hydrolysis of the anhydride moities. The properties of both hydrolyzed and nonhydrolyzed polymers were investigated. As demonstrated by light-scattering measurements in batch, the copolymers showed some level of aggregation in DMF, DMSO, and aqueous DMSO. The presence of aggregates was confirmed by size-exclusion chromatography in DMF. However, partial deaggregation occurred for the lowest molecular weight sample, on adding 1% w/v of LiBr. The nonhydrolyzed copolymers exhibited a rigid conformation in a 5% water/DMSO mixture, as well as their hydrolyzed counterpart at a low ionization degree. The rate of the hydrolysis reaction was shown to be dependent on the pH of the reaction medium and on temperature. The activation energy of the hydrolysis reaction was 14 kJ/mol, and the rate constant in the order of 10 Ϫ4 s Ϫ1 . On the basis of these data, the effect on the grafting reaction of biomolecules of different parameters such as ionic strength and the nature of the solvent, along with some other results were interpreted in terms of interactions between the synthetic and bioactive macromolecules.

Bioengineering Functional Copolymers. IX. Poly[(maleic anhydride‐co‐hexene‐1)‐g‐poly(ethylene oxide)]

“…The effect of different parameters such as ionic strength and the nature of solvent on the grafting reaction of biomolecules, along with some other results, have been interpreted in terms of the interactions of synthetic and bioactive macromolecules. [47] In this study, the effect of GA and BSA concentrations, the amount of copolymer, and the temperature and pH value were investigated for the determination of the optimum conditions during immobilization of invertase, both through direct binding and by using a spacer arm. The conjugation of the invertase enzyme may be correlated to the increase in the immobilized surface area obtained by using 0.1 g of copolymer only.…”

Drug release mechanisms of chemically cross-linked albumin microparticles: Effect of the matrix erosion

“…Vitamin B 12 (Vit-B 12 ) was used as the model drug. To obtain such a system, BSA was modified with maleic anhydride (MAy) in water, because only a small number of proteins may sustain dissolution in an organic medium without their molecular recognition properties being lost [16]. The nucleophilic groups in BSA, which could react with MA, are thiols of cysteine, hydroxyls of serine and tyrosine, and amines in the side chains of lysine [17].…”

Bioengineering functional copolymers. XII. Interaction of boron-containing and PEO branched derivatives of poly(MA-alt-MVE) with HeLa cells

“…It is known that these copolymers can be regarded as pre-activated polymers due to the presence of anhydride moieties susceptible to the reaction with a primary amine of a biomolecule [9]. The alternating copolymers of maleic anhydride (MA) with methyl vinyl ether (MVE) or divinyl ether (DVE) were utilized in various applications in diagnostics [10,11] and in chemotherapy as effective antitumor agents [8]. Poly (MA-alt-DVE), known as pyran copolymer is one of the well known bioengineering polymers having a wide range of biological activity.…”