|Title||Glycosaminoglycans are potential pharmacological targets for classic DNA minor groove binder drugs berenil and pentamidine.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Journal||Phys Chem Chem Phys|
|Date Published||2015 Oct 14|
It is shown that the antiprotozoal drugs berenil and pentamidine, conventional minor groove binders of DNA, form non-covalent complexes with polyanionic glycosaminoglycans. Induced circular dichroism (CD) spectra as well as UV hypochromism confirmed drug binding to the asymmetric template of heparin and chondroitin 6-sulfate. The biphasic nature of the CD signals refers to intermolecular chiral exciton coupling between the dicationic guest molecules forming a right- or a left-handed helical array along the GAG chains. Quantitative evaluation of the spectroscopic data measured in pH 7.0 buffer solution (80 mM NaCl) indicated a higher (Ka ∼ 10(6) M(-1) for berenil) and a lower (Ka ∼ 10(5) M(-1) for pentamidine) affinity heparin binding of these agents, similar to that reported for DNA. Drug-chondroitin sulfate complexes (Ka ∼ 10(4)-10(5) M(-1)) could be detected only at low ionic strength. These results imply that besides nucleic acids, GAGs may be another pharmacological targets for diarylamidine drugs.
|Alternate Journal||Phys Chem Chem Phys|