High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbituril Complexation.
Gubeli, Raphael J
van, der Walle Christopher F
Angewandte Chemie (International ed. in English)
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Sonzini, S., Marcozzi, A., Gubeli, R. J., van, d. W. C. F., Ravn, P., Herrmann, A., & Scherman, O. (2016). High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbituril Complexation.. Angewandte Chemie (International ed. in English), 55 14000-14004. https://doi.org/10.1002/anie.201606763
Supramolecular interactions between the host cucurbituril (CB) 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 (MV⋅CB) 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 complex, matching that of the cyclic peptide. By achieving selective CB-mediated conjugation of a small molecule to a recombinant protein scaffold we pave the way to biomedical applications of this simple ternary system.
European Research Council (Grant IDs: ASPiRe 240629, NUCLEOPOLY240080, STREPproject MICREAGENTS), Netherlands Organization for Scientific Research (Grant ID: NWO-Vici), Zernike Institute for Advanced Materials, MedImmune
European Research Council (240629)
External DOI: https://doi.org/10.1002/anie.201606763
This record's URL: https://www.repository.cam.ac.uk/handle/1810/261070