Interaction of 3,9-disubstituted acridine with single stranded poly(rA), double stranded poly(rAU) and triple stranded poly(rUAU): molecular docking - A spectroscopic tandem study

Chem Biol Interact. 2024 Mar 27:110965. doi: 10.1016/j.cbi.2024.110965. Online ahead of print.ABSTRACTRNA plays an important role in many biological processes which are crucial for cell survival, and it has been suggested that it may be possible to inhibit individual processes involved in many diseases by targeting specific sequences of RNA. The aim of this work is to determine the affinity of novel 3,9-disubstited acridine derivative 1 with three different RNA molecules, namely single stranded poly(rA), double stranded homopolymer poly(rAU) and triple stranded poly(rUAU). The results of the absorption titration assays show that the binding constant of the novel derivative to the RNA molecules was in the range of 1.7-6.2 × 104 mol dm-3. The fluorescence and circular dichroism titration assays revealed considerable changes. The most significant results in terms of interpreting the nature of the interactions were the melting temperatures of the RNA samples in complexes with the 1. In the case of poly(rA), denaturation resulted in a self-structure formation; increased stabilization was observed for poly(rAU), while the melting points of the ligand-poly(rUAU) complex showed significant destabilization as a result of the interaction. The principles of molecular mechanics were applied to propose the non-bonded interactions within the binding complex, penta-adenosylribonucleotide and acridine ligand as the study model. Initial molecular docking provided the input structure for adva...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Source Type: research