title: A Modular Synthesis of Conformationally Preorganised Extended β-Strand Peptidomimetics.
abstract: A promising strategy for mediating protein-protein interactions is the use of non-peptidic mimics of secondary structural protein elements, such as the α-helix. Recent work has expanded the scope of this approach by providing proof-of-principle scaffolds that are conformationally biased to mimic the projection of side-chains from one face of another common secondary structural element-the β-strand. Herein, we present a synthetic route that has key advantages over previous work: monomers bearing an amino acid side-chain were pre-formed before rapid assembly to peptidomimetics through a modular, iterative strategy. The resultant oligomers of alternating pyridyl and six-membered cyclic ureas accurately reproduce a recognition domain of several amino acid residues of a β-strand, demonstrated herein by mimicry of the i, i+2, i+4 and i+6 residues.
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://hamilton.chem.ox.ac.uk.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://hamilton.chem.ox.ac.uk.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Knipe
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://hamilton.chem.ox.ac.uk.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busschaert
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://hamilton.chem.ox.ac.uk. sam.thompson@chem.ox.ac.uk.
authors.forename: Sam
authors.initials: S
authors.lastname: Thompson
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://hamilton.chem.ox.ac.uk. andrew.hamilton@chem.ox.ac.uk.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hamilton
mesh_terms: D032701:Biomimetics; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry; D017433:Protein Structure, Secondary; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D010455:Peptides; D057786:Peptidomimetics; D014157:Transcription Factors
keywords: dipolar repulsion; extended conformations; foldamers; inhibitors; protein-protein interactions