title: Recapitulating the α-helix: nonpeptidic, low-molecular-weight ligands for the modulation of helix-mediated protein-protein interactions.
abstract: Protein-protein interactions play critical roles in a wide variety of biological processes, and their dysregulations contribute to the pathogenesis of several diseases, including cancer. Chemical entities that can abrogate aberrant protein-protein interactions may provide novel therapeutic agents. A large number of protein-protein interactions are mediated by protein secondary structure, the most commonly encountered form of which is the α-helix. Accordingly, over the last decade, there has been a flood of nonpeptidic small molecules that recapitulate the projection and chemical nature of key side chains of the canonical α-helix as a strategy to disrupt helix-mediated protein-protein interactions. In this review, we discuss recent advances (post 2006) in the design of synthetic α-helix mimetics, which include single-faced and two-faced/amphipathic structures, for the modulation of protein-protein interactions.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD 21201, USA.
authors.forename: Maryanna
authors.initials: M
authors.lastname: Lanning
authors.forename: Steven
authors.initials: S
authors.lastname: Fletcher
mesh_terms: D008024:Ligands; D018716:Molecular Mimicry; D008970:Molecular Weight; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D011506:Proteins