Inspired by natural transcription factors (TFs), researchers have explored the potential of artificial peptides for the recognition of specific DNA sequences, developing increasingly sophisticated systems that not only display excellent DNA binding properties, but also are endowed with new properties not found in their natural counterparts. Here we review some of the developments in the field of artificial peptide‐based DNA binders, focusing on the supramolecular and molecular design aspects of such systems.

We describe a lanthanide biosensor that responds to CDK4 kinase activity in melanoma cell extracts through a significant and dose dependent increase in luminescence, thanks to sensitization of a DOTA[Tb] complex incorporated into a CDK4 substrate peptide by a unique tryptophan residue in an adjacent phosphoaminoacid binding moiety.

A set of Ru(ii) metallopeptides containing the dppz ligand has been synthesized using SPPS methods. Fluorescence titration studies show that those metallopeptides featuring an octaarginine tail display a large binding preference for DNA G-quadruplex structures over those lacking it, and also that the interplay between the octoarginine functionalization and the ancillary ligand in the complex has an essential role in the recognition process. Furthermore, the oligoarginine metallopeptides are also efficiently internalized, causing cell death with signs of apoptosis.