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]arene polycations towards heparin. The recognition process was studied in comparison with two other heparin antagonists: protamine and polylysine. The arrangement of multiple functional groups on the flexible macrocyclic scaffold of calix[8]arene, with 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 that these calixarene derivatives have a very high specificity and affinity towards heparin neutralization as in aqueous solution as in blood. Analogous results were obtained with low molecular weight heparin (LMWH) whose effect protamine is unable to completely reverse.
Mecca
Tommaso
T
CNR-Istituto di Chimica Biomolecolare, Via del Santuario, 110, I-95028, Valverde (CT), Italy.
Consoli
Grazia M L
GM
Geraci
Corrada
C
La Spina
Rita
R
Cunsolo
Francesca
F
D000818:Animals; D001777:Blood Coagulation; D047250:Calixarenes / Q000737:chemistry*; D004801:Eosine Yellowish-(YS); D006495:Heparin, Low-Molecular-Weight / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D011479:Protamines / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013552:Swine; D013918:Thrombin Time; D017186:Titrimetry
D047250:Calixarenes; D004801:Eosine Yellowish-(YS); D006495:Heparin, Low-Molecular-Weight; D011073:Polyamines; D000071228:Polyelectrolytes; D011479:Protamines