High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation. Issue 45 (13th October 2016)

• Record Type: Journal Article
• Authors: Sonzini, Silvia; Marcozzi, Alessio; Gubeli, Raphael J.; van der Walle, Christopher F.; Ravn, Peter; Herrmann, Andreas; Scherman, Oren A.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 45(2016)
• Page Start: 14000
• Page End: 14004
• Publication Date: 2016-10-13
• Subjects: cucurbit[8]uril -- host–guest interactions -- molecular recognition -- protein engineering -- supramolecular chemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201606763
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : Protein engineering : Phage display was used to select amino acid motifs with highest binding affinity for the 1:1 methyl viologen–cucurbit[8]uril complex (MV⋅CB[8]). A three amino acid epitope was extrapolated from the selection rounds and incorporated into a protein domain, which exhibited micromolar binding affinity, leading to selective CB[8]‐mediated conjugation of a small molecule to a recombinant protein scaffold.