Binding of anti-prion agents to glycosaminoglycans: evidence from electronic absorption and circular dichroism spectroscopy.

TitleBinding of anti-prion agents to glycosaminoglycans: evidence from electronic absorption and circular dichroism spectroscopy.
Publication TypeJournal Article
Year of Publication2006
AuthorsZsila, F, Gedeon, G
JournalBiochem Biophys Res Commun
Volume346
Issue4
Pagination1267-74
Date Published2006 Aug 11
ISSN0006-291X
KeywordsAbsorption, Chondroitin Sulfates, Circular Dichroism, Glycosaminoglycans, Heparin, Prions, Quinacrine
Abstract

The polyanionic glycosaminoglycans (GAGs) are intimately involved in the pathogenesis of protein conformational disorders such as amyloidosis and prion diseases. Several cationic agents are known to exhibit anti-prion activity but their mechanism of action is poorly understood. In this study, UV absorption and circular dichroism (CD) spectroscopic techniques were used to investigate the interaction between heparin and chondroitin-6-sulfate and anti-prion drugs including acridine, quinoline, and phenothiazine derivatives. UV band hypochromism of (+/-)-quinacrine, (+/-)-primaquine, tacrine, quinidine, chlorpromazine, and induced CD spectra of (+/-)-quinacrine upon addition of GAGs provided evidence for the GAG binding of these compounds. The association constants (approximately 10(6)-10(7)M(-1)) estimated from the UV titration curves show high-affinity drug-heparin interactions. Ionic strength-dependence of the absorption spectra suggested that the interaction between GAGs and the cationic drugs is principally electrostatic in nature. Drug binding differences of heparin and chondroitin-6-sulfate were attributed to their different negative charge density. These results call the attention to the alteration of GAG-prion/GAG-amyloid interactions by which these compounds might exert their anti-prion/anti-amyloidogenic activities.

DOI10.1016/j.bbrc.2006.06.033
Alternate JournalBiochem. Biophys. Res. Commun.
PubMed ID16793017