Heparin-induced circular dichroism of an achiral, bicyclic species.
Antimalarial drugs have shown potential in suppressing the role of glycosaminoglycans (GAGs) in the pathology of prion protein conformational disorders (e.g. "Mad Cow" disease) by competing for sites of electrostatic interaction. In this study, circular dichroism (CD) and UV/Visible (UV/Vis) absorption spectroscopy techniques were used to investigate the interactions between N-methyl-N'-(7-chloro-4-quinolyl)-1,3-diaminopropane (QD), an achiral, bicyclic compound similar to previously investigated antimalarial drugs, and heparin, a complex GAG that is frequently used as a clinical anticoagulant. Relatively intense heparin-induced CD features were observed for QD and were noted to be radically different from previous studies using related chiral drugs, underscoring the importance of the Pfieffer effect on this and similar heparin research. Additionally, the induced CD for QD was observed to be highly dependent upon drug concentration, heparin concentration, system pH, equilibration time, and ionic strength. These results, in connection with recent work, provide new insight into the nature of the association between GAGs and antimalarial species.
Department of Chemistry, University of Cincinnati, Cincinnati, Ohio, USA.
Floyd E
FE
Stanley
Andrew M
AM
Warner
Kayla M
KM
McWilliams
Apryll M
AM
Stalcup
D000962:Antimalarials / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002738:Chloroquine / Q000031:analogs & derivatives / Q000737:chemistry; D002942:Circular Dichroism; D006493:Heparin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D009994:Osmolar Concentration; D012996:Solutions; D013237:Stereoisomerism
D000962:Antimalarials; D001643:Bridged Bicyclo Compounds; D012996:Solutions; D002738:Chloroquine; D006493:Heparin