title: High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation.
abstract: Supramolecular interactions between the host cucurbit[8]uril (CB[8]) and amino acids have been widely interrogated, but recognition of specific motifs within a protein domain have never been reported. A phage display approach was herein used to select motifs with the highest binding affinity for the heteroternary complex with methyl viologen and CB[8] (MV⋅CB[8]) within a vast pool of cyclic peptide sequences. From the selected motifs, an epitope consisting of three amino acid was extrapolated and incorporated into a solvent-exposed loop of a protein domain; the protein exhibited micromolar binding affinity for the MV⋅CB[8] complex, matching that of the cyclic peptide. By achieving selective CB[8]-mediated conjugation of a small molecule to a recombinant protein scaffold we pave the way to biomedical applications of this simple ternary system.
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.|Formulation Sciences, MedImmune Ltd., Granta Park, Cambridge, CB21 6GH, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sonzini
authors.affiliation: Zernike Institute for Advanced Materials, Dept. of Polymer Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
authors.forename: Alessio
authors.initials: A
authors.lastname: Marcozzi
authors.affiliation: Formulation Sciences, MedImmune Ltd., Granta Park, Cambridge, CB21 6GH, UK.
authors.forename: Raphael J
authors.initials: RJ
authors.lastname: Gubeli
authors.affiliation: Formulation Sciences, MedImmune Ltd., Granta Park, Cambridge, CB21 6GH, UK.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: van der Walle
authors.affiliation: Antibody Discovery and Protein Engineering, MedImmune Ltd., Granta Park, Cambridge, CB21 6GH, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Ravn
authors.affiliation: Zernike Institute for Advanced Materials, Dept. of Polymer Chemistry, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands. a.herrmann@rug.nl.
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK. oas23@cam.ac.uk.
authors.forename: Oren A
authors.initials: OA
authors.lastname: Scherman
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry*; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D000596:Amino Acids; D001952:Bridged-Ring Compounds; D000939:Epitopes; D007093:Imidazoles; D010456:Peptides, Cyclic; C507198:cucurbit(8)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
keywords: cucurbit[8]uril; host-guest interactions; molecular recognition; protein engineering; supramolecular chemistry