Interaction between\nthe Polyelectrolytes Unfractionated\nHeparin and Universal Heparin Reversal Agents

The interaction of unfractionated heparin (UFH) with\nuniversal\nheparin reversal agent 7 (UHRA-7) is investigated. UHRA-7 is composed\nof a hyperbranched polyglycerol core onto which an array of methylated\ntris(2-aminoethylamine) (Me-TREN) charged groups is grafted, which\nin turn are shielded with a layer of small chain poly(ethylene glycol)\nmethyl ether (mPEG) chains. This system has previously been shown\nto be biocompatible and to be effective at neutralizing heparin. The\nbinding constant <i>K</i><sub>b</sub> was determined from\nisothermal titration calorimetry experiments, at temperatures ranging\nfrom 278 to 323 K and salt concentrations ranging from 0.06 to 0.20\nM NaCl. The data were analyzed in terms of a number of different theoretical\nmodels to determine the contribution of counterion release and water\nrelease to driving the interaction between UFH and UHRA-7. With the\nsupport of NMR and molecular dynamics simulation data, a model of\nthe interaction between UFH and UHRA-7 is proposed. The binding of\nheparin and universal heparin reversal agent 7 is mainly due to charge–charge\ninteractions between the negatively charged units on UFH with positively\ncharged Me-TREN and mPEG chains.