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High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation
Author(s) -
Sonzini Silvia,
Marcozzi Alessio,
Gubeli Raphael J.,
van der Walle Christopher F.,
Ravn Peter,
Herrmann Andreas,
Scherman Oren A.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201606763
Subject(s) - epitope , chemistry , supramolecular chemistry , molecular recognition , phage display , peptide , amino acid , cyclic peptide , ternary complex , combinatorial chemistry , recombinant dna , stereochemistry , biochemistry , molecule , biology , antigen , organic chemistry , genetics , gene , enzyme
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.