PPII Helical Peptidomimetics Templated by Cation–π Interactions. (19th August 2016)

• Record Type: Journal Article
• Authors: Craven, Timothy W.; Bonneau, Richard; Kirshenbaum, Kent
• Is Part Of: Chembiochem. Volume 17:Number 19(2016)
• Page Start: 1824
• Page End: 1828
• Publication Date: 2016-08-19
• Subjects: foldamers -- miniature protein design -- peptoids -- PPII helices -- PXXP motif mimetics; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600248
• Languages: English
• ISSNs: 1439-4227

Abstract

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. Abstract : PPII helices on lockdown : A network of cation–π interactions was used to template peptide and peptoid residues into left‐handed poly‐proline type II (PPII) helices, covalently locking the secondary structure with an engineered disulfide bridge. These chemically diverse PPII helical structures provide a new route toward peptidomimetic protein–protein interaction inhibitors.