Biomacromolecule Recognition by Calixarene Macrocycles.

After having been extensively studied as a receptor for small guests (both neutral and charged), the last 20 years have witnessed the progressive use of the calixarene macrocycle as a ligand for the recognition of large biomacromolecules. Thanks to the easy functionalization of both rims, to the multivalent nature of the scaffold, and to the possibility of controlling its three-dimensional shape and conformation, a number of calixarene derivatives able to selectively interact with proteins (including specific areas of a protein surface or an active site) or with nucleic acids have been reported. This review critically covers the results obtained in the field of biomacromolecule recognition by calixarene derivatives, giving a special emphasis to those examples where the interaction with the target leads to a specific and potentially medically relevant activity, such as protein inhibition, disruption of protein-protein interactions, and gene delivery.