Title
Small Molecule Induced Poly(A) Single Strand to Self-Structure Conformational Switching: Evidence for the Prominent Role of H-bonding Interactions
Author
Sabyasachi Chatterjee, Gopinatha Suresh Kumar
Year
2017
Journal
Molecular BioSystems
Abstract
All messenger RNAs (mRNA) have a polyadenylic acid tail that is added during the post transcriptional RNA processing. Investigations on the structure-function and interaction of polyadenylic acid is an important area to target for cancer and related diseases. Jatrorrhizine and coptisine are two important isoquinoline alkaloids, structurally very similar, differing only in substitutents on the isoquinoline chromophore. Here we demonstrate that these alkaloids differentailly induce self-structure in single stranded poly(A) from absorbance, thermal melting and differential scanning calorimetry experiments. Jatrorrhizine was found to be more effective than coptisine in binding to poly(A) from spectroscopy and calorimetry data. Molecular modeling results suggested the involvement of more H-bonds in the complexation of former with poly(A). It appears that the presence of substituents on the alkaloid that can H-bonds with the adenine nucelotides play critical role in the binding and structural rearrangement of poly(A) to self-structure. The atomic force microscopy data directly visualized the poly(A) self-structured network. We propose a plausible mechanism of the small molecule induced self-structure formation in poly(A). The results presented here may help in the design of effective poly(A) targeted molecules for therapeutic use.
Instrument
J-815
Keywords
Circular dichroism, Induced CD, RNA structure, Ligand binding, Biochemistry