The evolving world of protein-G-quadruplex recognition: A medicinal chemist’s perspective

The physiological and pharmacological role of nucleic acids structures folded into the non canonical G-quadruplex conformation have recently emerged. Their activities are targeted at vital cellular processes including telomere maintenance, regulation of transcription and processing of the pre-messenger or telomeric RNA. In addition, severe conditions like cancer, fragile X syndrome, Bloom syndrome, Werner syndrome and Fanconi anemia J are related to genomic defects that involve G-quadruplex forming sequences. In this connection G-quadruplex recognition and processing by nucleic acid directed proteins and enzymes represents a key event to activate or deactivate physiological or pathological pathways. In this review we examine protein-G-quadruplex recognition in physiologically significant conditions and discuss how to possibly exploit the interactions’ selectivity for targeted therapeutic intervention.

► G-quadruplex DNA and RNA structures interact efficiently with a variety of proteins.
► G-quadruplex protein recognition allows development of selective aptamers/antibodies.
► G-quadruplex-protein complexes can be exploited as unique drug targets.