title: Receptor-templated stapling of intrinsically disordered peptide ligands.
abstract: We report here a chemoselective peptide "stapling" method that can be performed on ligand-receptor complexes in situ. An appropriately structured macrocyclic bis-oxime linkage is shown to improve the affinity of a peptide ligand for its native protein receptor. The presence of the receptor as a template to preorganize the ligand into its bioactive conformation is found to bias reaction outcomes, suggesting the potential application of the method for receptor-assisted selection of stapled peptides.
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA. horne@pitt.edu.
authors.forename: Conor M
authors.initials: CM
authors.lastname: Haney
authors.forename: W Seth
authors.initials: WS
authors.lastname: Horne
mesh_terms: D000595:Amino Acid Sequence; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010091:Oximes / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D064267:Intrinsically Disordered Proteins; D008024:Ligands; D010091:Oximes; D010455:Peptides