Izvestiya of Saratov University.

Chemistry. Biology. Ecology

ISSN 1816-9775 (Print)
ISSN 2541-8971 (Online)

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Complexation of Polymyxin B1 Derivatives with Heparin

Shalygina Violetta V., Institute of high molecular compounds RAS
Vlasova Elena N., Institute of high molecular compounds RAS
Anan'eva Elena P., Saint Petersburg state University of chemistry and pharmacy
Gurina Svetlana V., Saint Petersburg state University of chemistry and pharmacy

The method of coprecipitation from aqueous solutions at a neutral pH value was used to study the interaction of polymyxin B1 derivatives with sodium heparinate. They were compared with the initial unmodified antibiotic and with the initial antibiotic in a solution of the corresponding polymer, covalently unbound with it. It was observed that intense precipitation for an unmodified antibiotic took place at a 10-fold molar excess of the peptide by the base (the expected mole of heparin is 12000–16000, polymyxin B1 base – 1150), the temperature of 37° С and the low ionic strength of the solution. It was found that for the examined derivatives obtained by modifying polymyxin B1 at amino groups with synthetic water-soluble polymers, the amount of precipitate at the same pH level and ionic strength at any peptidesodium heparinate ratios was significantly less and did not depend on the temperature during the experiment. Using IR spectroscopy it was confirmed that both carboxyl and sulfamide groups of heparin were involved in complexation. Differences in the nature of the interaction of sodium heparinate with the initial peptide and its derivatives were revealed. The observed lower affinity of heparin binding to polymyxin B1 derivatives compared to the initial antibiotic was apparent due to decrease in the density of positive charge localization in their molecule as a result of modification of -NH2 groups.


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