The Mechanism of Dynamic Interaction between Doxorubicin and Calf Thymus DNA at the Single-Molecule Level Based on Confocal Raman Spectroscopy.

Abstract

It is of great fundamental significance and practical application to understand the binding sites and dynamic process of the interaction between doxorubicin (DOX) and DNA molecules. Based on the Confocal Raman spectroscopy, the interaction between DOX and calf thymus DNA has been systemically investigated, and some meaningful findings have been found. DOX molecules can not only interact with all four bases of DNA molecules, i.e., adenine, thymine, cytosine, guanine, and phosphate, but also affect the DNA conformation. Meanwhile, the binding site of DOX and its derivatives such as daunorubicin and epirubicin is certain. Furthermore, the interaction between DOX and DNA molecules is a dynamic process since the intensities of each characteristic peaks of the base, e.g., adenine, cytosine, and phosphate, are all regularly changed with the interaction time. Finally, a dynamic mechanism model of the interaction between DOX and DNA molecules is proposed; that is, there are two kinds of interaction between DOX and DNA molecules: DOX-DNA acts to form a complex, and DOX-DOX acts to form a multimer. The two effects are competitive, as the former compresses DNA molecules, and the latter decompresses these DNA molecules. This work is helpful for accurately understanding and developing new drugs and pathways to improve and treat DOX-induced cytotoxicity and cardiotoxicity.