Conformational energetics of insulin in interpolyelectrolyte complexes insulin-poly(methylaminophosphazene) under near-physiological conditions

Interaction of a synthetic biodegradable polymer, poly(methylaminophosphazene), (PMAP) with human recombinant zinc insulin at pH 7.4 and different ionic strengths was studied by means of turbidimetry, phase analysis and high-sensitivity differential scanning calorimetry. The formation of stoichiometric (insoluble) and non-stoichiometric (soluble) interpolyelectrolyte Insulin-PMAP complexes was detected. It was shown that binding of zinc insulin to PMAP is accompanied by conversion of the protein to its zinc-free form as a result of the Zn+2 release from the insulin native structure. The conformational stability of the bound zinc-free insulin is defined by composition of the complexes. It increases in case of the non-stoichiometric complexes and decreases in the stoichiometric ones. We found that soluble Insulin-PMAP complexes revealed thermoresponsive properties within physiological range of temperature and ionic strength.