Use of Differential Scanning Calorimetry (DSC) to Study the Thermodynamics of DNA-Based Interactions and Nucleic Acid-Based Therapeutics

Abstract

In the 1950’s, the research findings of James Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins led to the discovery of the deoxyribonucleic acid (DNA) double-helix conformation [1,2]. With DNA at their core, many nucleic acid based assays are used in pharmaceutical, biochemistry, biotechnology, molecular biology, target-based drug design, and other DNA-based technologies [3-7]. In addition, DNA is the molecular target of numerous anti-tumor drugs, anti-viral drugs, and several anti-bacterial agents [8-10]. Historically there have been several approaches in developing some pharmacological and therapeutic agents that interfere with DNA synthesis [8,11]. Since the therapeutic effects of many DNA-binding interactions correlate with thermodynamic profiles of the resulting complexes, elucidation of thermodynamic parameters of such interactions are important in nucleic acid-based therapeutics [12,13]. Differential Scanning Calorimetry (DSC), which provides unique complementary information for nucleic acids, modified nucleic acids, and nucleic acid-ligand interactions, is a powerful method in obtaining thermodynamic parameters. DSC is a direct, model-independent measurement tool that complements, structural and bonding information obtained by various physicochemical methods [13-15]. This review is designed to give the reader a greater understanding of the applications of DSC in DNA-based therapeutics. While this review focuses on calorimetry studies of DNA-based complexes, DSC applications in RNAs have been reviewed elsewhere [16-18].