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Small molecule induced poly(A) single strand to self-structure conformational switching: evidence for the prominent role of H-bonding interactions

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Title Small molecule induced poly(A) single strand to
self-structure conformational switching: evidence
for the prominent role of H-bonding interactions
 
Creator Chatterjee, Sabyasachi
Kumar, Gopinatha Suresh
 
Subject Chemistry
 
Description All messenger RNAs (mRNAs) have a polyadenylic acid tail that is added during post transcriptional RNA
processing. Investigation of the structure–function and interactions of polyadenylic acid is an important
area to target for cancer and related diseases. Jatrorrhizine and coptisine are two important isoquinoline
alkaloids that are structurally very similar, differing only in the substituents on the isoquinoline chromophore.
Here we demonstrate that these alkaloids differentially induce a self-structure in single stranded
poly(A) using 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 the former with poly(A). It appears that the presence of substituents on the alkaloid that
can form H-bonding interactions with the adenine nucleotides may play a critical role in the binding and
structural rearrangement of poly(A) into the 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.
 
Date 2017-03-28
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2665/1/Mol._BioSyst.%2C_2017%2C_13.pdf
Chatterjee, Sabyasachi and Kumar, Gopinatha Suresh (2017) Small molecule induced poly(A) single strand to self-structure conformational switching: evidence for the prominent role of H-bonding interactions. Molecular-Biosystems, 13.
 
Relation http://dx.doi.org/10.1039/c7mb00031f
http://www.eprints.iicb.res.in/2665/