Protein bioconjugation is an increasingly important field of research, with wide-ranging applications in areas such as therapeutics and biomaterials. Traditional cysteine and lysine bioconjugation strategies are widely used and have been extensively researched, but in some cases they are not appropriate and alternatives are needed or they are not compatible with one another to enable the formation of dually (and distinctly) modified dual-conjugates (an increasingly desired class of bioconjugates). Here we review the heretofore less explored approach of tyrosine bioconjugation, which is rapidly becoming a constructive alternative/complement to the more well-established strategies. Herein we present an overview of the field, and then focus on promising recent methods that can achieve high conversion and chemoselectivity. This suggests that not only can tyrosine bioconjugation be used in conjunction with cysteine and lysine modification to obtain proteins with multiple different modifications, it is also becoming a stand-alone alternative to these more traditional methods.
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http://dx.doi.org/10.1039/d0ob01912g | DOI Listing |
Mol Omics
December 2024
Department of Chemistry and Biochemistry, University of Texas at Arlington, Box 19065, 700 Planetarium Place, Room 130, Arlington, TX 76019, USA.
Designing reagents for protein labeling is crucial for investigating cellular events and developing new therapeutics. Historically, much effort has been focused on labeling lysine and arginine residues due to their abundance on the protein periphery. The chemo-selectivity of these reagents is a challenging yet crucial parameter for deciphering properties specifically associated with the targeted amino acid.
View Article and Find Full Text PDFBull Cancer
December 2024
Département de biologie expérimentale des tumeurs, institut de carcinogenèse, centre national de recherche médicale en oncologie N.N. Blokhin, ministère de la Santé de Russie, 24 Kashirskoe shosse, Moscou 115522, Fédération de Russie. Electronic address:
In 2023, the journals "Bioconjugate Chemistry" and "Sensors and Actuators B: Chemical" published two papers describing new biosensors for imaging hypoxic regions in tumors. Cao et al. combined acetazolamide (AZA) to target carbonic anhydrase IX (CA IX) with two tyrosine-derived Mn(II)-ethylenediaminetetraacetic acid chelates (TyEDTA) on a rigid triazine (TA) scaffold.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
November 2024
Department of Chemistry, University of California, Berkeley, Berkeley, CA-94720, USA.
Controlled modifications of amino acids are an indispensable tool for advancing fundamental and translational research based on peptides and proteins. Yet, we still lack methods to chemically modify each naturally occurring amino acid sidechain. To help address this gap, we show that N,α-diaryl oxaziridines expand the scope of bioconjugation methods to chemically modify cysteine, methionine, and tryptophan residues with evidence for additional tyrosine labelling in a proteomic context.
View Article and Find Full Text PDFPharmaceuticals (Basel)
September 2024
Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
: The incorporation of radionuclides into peptides and larger biomolecules requires efficient and sometimes biorthogonal reaction conditions, to which click chemistry provides a convenient approach. : Traditionally, click-based radiolabeling techniques have focused on classical click chemistry, such as copper(I)-catalyzed alkyne-azide [3+2] cycloaddition (CuAAC), strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC), traceless Staudinger ligation, and inverse electron demand Diels-Alder (IEDDA). : However, newly emerging click-based radiolabeling techniques, including tyrosine-click, sulfo-click, sulfur(VI) fluoride exchange (SuFEx), thiol-ene click, azo coupling, hydrazone formations, oxime formations, and RIKEN click offer valuable alternatives to classical click chemistry.
View Article and Find Full Text PDFBioconjug Chem
September 2024
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal.
Ferritin (Ft) nanoparticles have become versatile platforms for displaying antigens, being a promising technology for vaccine development. While genetic fusion has traditionally been the preferred method for antigen display, concerns about improper folding and steric hindrance that may compromise vaccine efficacy or stability have prompted alternative approaches. Bioconjugation offers the advantage of preserving native protein structure and function, with recent advancements improving efficiency and specificity.
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