title: α-Helix mimetics: outwards and upwards.
abstract: α-Helices are common secondary structural elements forming key parts of the large, generally featureless interfacial regions of many therapeutically-relevant protein-protein interactions (PPIs). The rational design of helix mimetics is an appealing small-molecule strategy for the mediation of aberrant PPIs, however the first generation of scaffolds presented a relatively small number of residues on a single recognition surface. Increasingly, helices involved in PPIs are found to have more complex binding modes, utilizing two or three recognition surfaces, or binding with extended points of contact. To address these unmet needs the design and synthesis of new generations of multi-sided, extended, and supersecondary structures are underway.
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, UK.
authors.forename: Madura K P
authors.initials: MK
authors.lastname: Jayatunga
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, UK. Electronic address: sam.thompson@chem.ox.ac.uk.
authors.forename: Sam
authors.initials: S
authors.lastname: Thompson
authors.affiliation: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX1 3TA, UK. Electronic address: andrew.hamilton@chem.ox.ac.uk.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D001665:Binding Sites; D032701:Biomimetics / Q000639:trends; D002147:Calmodulin / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D017433:Protein Structure, Secondary
chemical_list: D002147:Calmodulin
keywords: Peptidomimetic; Protein–protein interaction; Proteomimetic; Rational design