Molecular recognition of poly(A) targeting by protoberberine alkaloids: in vitro biophysical studies and biological perspectives

The use of small molecules to specifically control important cellular functions through binding to nucleic acids is an area of major current interest at the interface of chemical biology and medicinal chemistry. The polyadenylic acid [poly(A)] tail of mRNA has been recently established as a potential drug target due to its significant role in the initiation of translation, maturation and stability of mRNA as well as in the production of alternate proteins in eukaryotic cells. Very recently some small molecule alkaloids of the isoquinoline group have been found to bind poly(A) with remarkably high affinity leading to self-structure formation. Plant alkaloids are small molecules known to have important traditional roles in medicinal chemistry due to their extensive biological activity. Especially, noteworthy are the protoberberine alkaloids that are widely distributed in several botanical families exhibiting myriad therapeutic applications. This review focuses on the structural and biological significance of poly(A) and interaction of protoberberine alkaloids with this RNA structure for the development of new small molecule alkaloids targeted to poly( A) structures as futuristic therapeutic agents.