title: Macrocycles as protein-protein interaction inhibitors.
abstract: Macrocyclic compounds such as cyclic peptides have emerged as a new and exciting class of drug candidates for inhibition of intracellular protein-protein interactions, which are challenging targets for conventional drug modalities (i.e. small molecules and proteins). Over the past decade, several complementary technologies have been developed to synthesize macrocycle libraries and screen them for binding to therapeutically relevant targets. Two different approaches have also been explored to increase the membrane permeability of cyclic peptides. In this review, we discuss these methods and their applications in the discovery of macrocyclic compounds against protein-protein interactions.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, U.S.A.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Dougherty
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, U.S.A.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, U.S.A. pei.3@osu.edu.
authors.forename: Dehua
authors.initials: D
authors.lastname: Pei
mesh_terms: D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D001692:Biological Transport; D002463:Cell Membrane Permeability / Q000187:drug effects; D004058:Diffusion; D055808:Drug Discovery; D005057:Eukaryotic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047668:Inteins / Q000187:drug effects; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D001688:Biological Products; D019151:Peptide Library; D010456:Peptides, Cyclic; D011506:Proteins; D054852:Small Molecule Libraries
keywords: cell-penetrating peptide; cyclic peptide; drug discovery; macrocycle; protein–protein interaction; undruggable targets