Polycationic calix[8]arenes able to recognize and neutralize heparin

A mutual induced fit mechanism is responsible for the exceptional complexation performances exhibited by calix[8]arenes polycations towards heparin. The recognition process was studied in comparison with other two different heparin antagonists: protamine and polylysine. The arrangement of multiple functional groups on the flexible macrocyclic scaffold of calix[8]arene, in respect to the conformationally rigid protamine and low ordered polylysine, allowed a mutual adaptability between calixarene polycations and heparin, significantly enhancing the recognition performances. Fluorescence, NMR titration, and activated partial thromboplastin time (aPTT) experiments confirmed the high specificity and affinity of these calixarene derivatives towards heparin neutralization in water medium as in blood. Analogous results were obtained with low molecular weight heparin (LMWH) whose effect protamine is unable to completely reverse