Heparin-polypeptide interactions in aqueous solution

Abstract

Circular dichroism spectroscopy has been used to study the interactions between heparin and cationic polypeptides in dilute aqueous solution at neutral pH. The results indicate that poly( l-lysine), poly( l-arginine), and poly( l-ornithine) adopt the α-helical conformation in the presence of heparin, rather than the “charged coil” form observed for the polypeptide alone under the same conditions. Maximum interaction for the poly( l-lysine) and poly( l-ornithine) systems occur at an amino acid: disaccharide residue ratio of 2.3 ± 0.1:1, which correlates with the analytical data of 2.3 sulfates per heparin disaccharide. For poly( l-arginine), maximum interaction occurs at a residue ratio of 3.3 ± 0.1:1, and indicates that all the anionic groups (sulfate and carboxyl) of the heparin are involved in this case. The interactions of heparin are analogous to those observed previously for six connective tissue mucopolysaccharides, except that none of the latter had any effect on the conformation of poly( l-ornithine). The poly( l-ornithine)-heparin system shows a thermal “melting” transition at T m = 56.0 ± 1.0 ° C, at which point the polypeptide reverts to the “charged coil” form; the interactions with poly( l-lysine) and poly( l-arginine) are stable up to temperatures > 90 °C. The high thermal stability of these conformation-directing effects indicate a stronger interaction for heparin than the other mucopolysaccharides, which is probably due to the high sulfate content.