Natural and Synthetic Oligoarylamides: Privileged Structures for Medical Applications

Abstract

The term "privileged structure" refers to a single molecular substructure or scaffold that can serve as a starting point for high-affinity ligands for more than one receptor type. In this report, a hitherto overlooked group of privileged substructures is addressed, namely aromatic oligoamides, for which there are natural models in the form of cystobactamids, albicidin, distamycin A, netropsin, and others. The aromatic and heteroaromatic core, together with a flexible selection of substituents, form conformationally well-defined scaffolds capable of specifically binding to conformationally well-defined regions of biomacromolecules such as helices in proteins or DNA often by acting as helices mimics themselves. As such, these aromatic oligoamides have already been employed to inhibit protein-protein and nucleic acid-protein interactions. This article is the first to bring together the scattered knowledge about aromatic oligoamides in connection with biomedical applications.

Keywords: DNA-binding; aromatic oligoamides; cystobactamids; dystamycin; foldamers; protein-protein interactions.