Nucleic acids exist in a dynamic equilibrium with a number of molecules that constantly interact with them and regulate the cellular activities. The inherent nature of the structure and conformational integrity of these macromolecules can lead to altered biological activity through proper targeting of nucleic acids binding ligands or drug molecules. We studied the interaction of naturally occurring methylxanthines such as theophylline, theobromine and caffeine with DNA, using UV absorption and Fourier transform infrared (FTIR) spectroscopic methods, and especially monitored their binding affinity in the presence of Mg2+ and during helix-coil transitions of DNA by temperature (Tm) or pH melting profiles. The study indicates that all these molecules effectively bind to DNA in a dose dependent manner. The overall binding constants of DNA-theophylline = 3.5×103 M−1, DNA-theobromine = 1.1×103 M−1, and DNA-Caffeine = 3.8×103 M−1. On the other hand Tm/pH melting profiles showed 24–35% of enhanced binding activity of methylxanthines during helix-coil transitions of DNA rather than to its native double helical structure. The FTIR analysis divulged that theophylline, theobromine and caffeine interact with all the base pairs of DNA (A-T; G-C) and phosphate group through hydrogen bond (H-bond) interaction. In the presence of Mg2+, methylxanthines altered the structure of DNA from B to A-family. However, the B-family structure of DNA remained unaltered in DNA-methylxanthines complexes or in the absence of Mg2+. The spectral analyses indicated the order of binding affinity as “caffeine≥theophylline>theobromine” to the native double helical DNA, and “theophylline≥theobromine>caffeine to the denatured form of DNA and in the presence of divalent metal ions.

GNRA tetraloops, found in high frequency in natural RNAs, make loop-receptor interactions, stabilizing the tertiary structure of Group I introns, a class of small RNAs. Analyzing 230 Group I introns, to study the distribution and sequence pattern of the GNRA tetraloops, we suggest that these features reflect the ancestral nature of these catalytic molecules, in a prebiotic RNA world. The adenosine rich GNRA tetraloops would have interacted with each other through long range RNA-RNA interactions to form higher order structures forming potential sites that render the propensity for the short RNAs to bind to metal ions from the prebiotic pool, aiding them to act as metalloenzymes.

The crystal structure determination of antibiotic binding sites on the 30S ribosomal subunit and the increasing demand for developing RNA-based drugs has prompted us to study the direct binding of spectinomycin, vancomycin and bleomycin with yeast total RNA using Fourier transform infrared (FTIR) spectroscopy. We report that the OH of spectinomycin and the peptide group of vancomycin can bind to the bases of RNA, which might depend on Mg2+ concentration. Bleomycin on the other hand does not show such a drastic effect on yeast total RNA. This study might help in developing innovative strategies utilizing RNA molecules to perform a variety of essential biological functions.