Foldamers as Anticancer Therapeutics: Targeting Protein-Protein Interactions and the Cell Membrane

Abstract

Targeting important protein-protein interactions involved in carcinogenesis or targeting the cell membrane of a cancer cell directly are just two of the ways in which foldamers (oligomeric molecules which fold into distinct shapes in solution) hold considerable potential in the treatment of cancer. By mimicking the local topography of the helical compound of interest using covalently constrained foldamers through to mimicking the topography of the natural helix such that the positions of key functional motifs are in an identical spatial orientation to match those presented by the original α-helix, synthetic foldamers have been used to mimic natural foldamers which interact with proteins or the cell membrane. Over a time-frame expanding more than a decade, these targeted approaches have become established, confirming their continued inclusion in the assortment of cancer targets being studied and the arsenal of chemotherapy compounds in development. These approaches are reviewed herein.