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π-Clamp-Mediated Homo- and Heterodimerization of Single-Domain Antibodies via Site-Specific Homobifunctional Conjugation

Ross Taylor, Mauricio Aguilar Rangel, Michael B. Geeson, Pietro Sormanni, Michele Vendruscolo, Gonçalo J. L. Bernardes

2022Journal of the American Chemical Society24 citationsDOIOpen Access PDF

Abstract

= 8-15 nM). When two solvent-exposed cysteine residues were present on the second protein domain, the π-clamp cysteine residue was selectively modified over an Asp-Cys-Glu cysteine residue, allowing for subsequent small-molecule conjugation. With this strategy, we build molecule-protein-protein conjugates with complete chemical control over the sites of modification.

Topics & Concepts

ChemistryCysteineResidue (chemistry)ConjugateFusion proteinBiophysicsStereochemistryBiochemistryCombinatorial chemistryRecombinant DNAEnzymeBiologyMathematical analysisGeneMathematicsMonoclonal and Polyclonal Antibodies ResearchClick Chemistry and ApplicationsPeptidase Inhibition and Analysis