Interaction between the Polyelectrolytes Unfractionated Heparin and Universal Heparin Reversal Agents.

The interaction of unfractionated heparin (UFH) with universal heparin reversal agent 7 (UHRA-7) is investigated. UHRA-7 is composed of a hyperbranched polyglycerol core onto which an array of methylated tris(2-aminoethylamine) (Me-TREN) charged groups is grafted, which in turn are shielded with a layer of small chain poly(ethylene glycol) methyl ether (mPEG) chains. This system has previously been shown to be biocompatible and to be effective at neutralizing heparin. The binding constant Kb was determined from isothermal titration calorimetry experiments, at temperatures ranging from 278 to 323 K and salt concentrations ranging from 0.06 to 0.20 M NaCl. The data were analyzed in terms of a number of different theoretical models to determine the contribution of counterion release and water release to driving the interaction between UFH and UHRA-7. With the support of NMR and molecular dynamics simulation data, a model of the interaction between UFH and UHRA-7 is proposed. The binding of heparin and universal heparin reversal agent 7 is mainly due to charge-charge interactions between the negatively charged units on UFH with positively charged Me-TREN and mPEG chains.