Glycosaminoglycans are potential pharmacological targets for classic DNA minor groove binder drugs berenil and pentamidine

Physical Chemistry Chemical Physics : PCCP
Ferenc Zsila

Abstract

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.

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Citations

Dec 12, 2020·The Journal of Physical Chemistry. B·Ferenc ZsilaMartyna Maszota-Zieleniak
Jun 26, 2020·Journal of Chemical Theory and Computation·Alireza Marefat KhahChristof Hättig
Sep 10, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Atanu NandySaptarshi Mukherjee

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