title: PPII Helical Peptidomimetics Templated by Cation-π Interactions.
abstract: Poly-proline type II (PPII) helical PXXP motifs are the recognition elements for a variety of protein-protein interactions that are critical for cellular signaling. Despite development of protocols for locking peptides into α-helical and β-strand conformations, there remains a lack of analogous methods for generating mimics of PPII helical structures. We describe herein a strategy to enforce PPII helical secondary structure in the 19-residue TrpPlexus miniature protein. Through sequence variation, we showed that a network of cation-π interactions could drive the formation of PPII helical conformations for both peptide and N-substituted glycine peptoid residues. The achievement of chemically diverse PPII helical scaffolds provides a new route towards discovering peptidomimetic inhibitors of protein-protein interactions mediated by PXXP motifs.
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, NY, 10003, USA.|Department of Biology, Center for Genomics and Systems Biology, New York University, 12 Waverly Pl., New York, NY, 10003, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Craven
authors.affiliation: Department of Biology, Center for Genomics and Systems Biology, New York University, 12 Waverly Pl., New York, NY, 10003, USA.|Department of Computer Science, Courant Institute of Mathematical Sciences, New York University, New York, NY, 10003, USA.|Simons Center for Data Analysis, 160 5th Ave., New York, NY, 10010, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.affiliation: Department of Chemistry, New York University, 100 Washington Square East, New York, NY, 10003, USA. twc254@nyu.edu.
authors.forename: Kent
authors.initials: K
authors.lastname: Kirshenbaum
mesh_terms: D002412:Cations / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D057786:Peptidomimetics; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D002412:Cations; D010455:Peptides; D057786:Peptidomimetics; C011083:polyproline
keywords: PPII helices; PXXP motif mimetics; foldamers; miniature protein design; peptoids