Bioconjugation techniques are methods that covalently connect a biomolecule to another molecular component while retaining the structural features required for its biological activity [1]. Protein and peptide conjugation can target endogenous amino acid side chains or terminal groups, with reaction selectivity governed by functional group reactivity and accessibility [1][2]. Cysteine thiols and lysine amino groups provide common attachment sites, although other residues can also participate in selective transformations [2]. Reactive groups may instead be introduced before conjugation to distinguish the intended site from competing functionalities [1]. Carbonyl groups react with aminooxy or hydrazine derivatives to form oximes or hydrazones, respectively; substrate structure and catalysis affect reaction rates and product stability [3]. Azide-based ligations provide another route to joining components through installed chemical handles [4]. The resulting conjugate may contain one defined attachment site or a distribution of modified sites. Reaction medium, stoichiometry, and chemical compatibility shape both the efficiency of coupling and the molecular composition of the product [1][2][3].
- site-selective conjugation
- cysteine modification
- oxime ligation
- chemical handles
References
- Omar Boutureira; Gonçalo J. L. Bernardes; Advances in Chemical Protein Modification. Chem. Rev. 2015, 115, 2174-2195, 10.1021/cr500399p.
- Oleksandr Koniev; Alain Wagner; Developments and recent advancements in the field of endogenous amino acid selective bond forming reactions for bioconjugation. Chem. Soc. Rev. 2015, 44, 5495-5551, 10.1039/c5cs00048c.
- Dominik K. Kölmel; Eric T. Kool; Oximes and Hydrazones in Bioconjugation: Mechanism and Catalysis. Chem. Rev. 2017, 117, 10358-10376, 10.1021/acs.chemrev.7b00090.
- Christine I. Schilling; Nicole Jung; Moritz Biskup; Ute Schepers; Stefan Bräse; Bioconjugation via azide–Staudinger ligation: an overview. Chem. Soc. Rev. 2011, 40, 4840-4871, 10.1039/c0cs00123f.