Deciphering the interactions between chlorambucil and calf thymus DNA: a multi-spectroscopic and molecular docking study.

Sayeed Ur Rehman, Tarique Sarwar, Hassan Mubarak Ishqi, Mohammed Amir Husain, Ziaul Hasan, Mohammad Tabish

Index: Arch. Biochem. Biophys. 566 , 7-14, (2015)

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Abstract

Non-covalent interactions of chlorambucil with calf thymus DNA was investigated using multi-spectroscopic techniques and molecular docking study. Binding constant calculated was found to be 1.54×10(4)M(-1) at 290K, significantly lower than various known intercalators. Quenching process was found to be static as evident by biomolecular quenching constant. Thermodynamic parameters revealed the involvement of hydrophobic interactions and hydrogen bonds in the binding. Chlorambucil was found to interact via external binding mode and follow groove binding as it replaces Hoechst (a typical groove binder) from the groove of DNA but does not replace intercalating dyes including ethidium bromide and acridine orange from the DNA helix. These results were further supported by KI quenching experiments, DNA melting studies, CD spectroscopy and molecular docking. Copyright © 2014 Elsevier Inc. All rights reserved.