Oligonucleotide-based systems for input-controlled and non-covalently regulated protein binding

Supramolecular chemists continuously take inspiration from complex biological systems to develop functional molecules involved in molecular recognition and self-assembly. In this regard, ‘smart’ synthetic molecules that emulate allosteric proteins are both exciting and challenging, because many allosteric proteins can be considered as molecular switches that bind to other protein targets in a non-covalent fashion and, importantly, are capable of having their output activity controlled by prior binding to input molecules. This review discusses the foundations and passage towards the development of non-covalently operated oligonucleotide-based systems with protein-binding capacity that can be precisely regulated in an input-controlled manner.