Repository logo
 

High Affinity Recognition of a Selected Amino Acid Epitope within a Protein by Cucurbit[8]uril Complexation.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Sonzini, Silvia 
Marcozzi, Alessio 
Gubeli, Raphael J 
van der Walle, Christopher F 
Ravn, Peter 

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.

Description

Keywords

cucurbit[8]uril, host-guest interactions, molecular recognition, protein engineering, supramolecular chemistry, Amino Acids, Bridged-Ring Compounds, Epitopes, Imidazoles, Molecular Structure, Peptides, Cyclic

Journal Title

Angew Chem Int Ed Engl

Conference Name

Journal ISSN

1433-7851
1521-3773

Volume Title

55

Publisher

Wiley
Sponsorship
Engineering and Physical Sciences Research Council (EP/K039520/1)
European Research Council (240629)
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