Protein–Protein Conjugates: Tyrosine Delivers

Geeson, Michael B.; Bernardes, Gonçalo J. L.

doi:10.1021/acscentsci.0c01008

Cited by 6 publications

(3 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Later work discovered that the ortho -quinone functional group generated upon tyrosine oxidation undergoes a reaction with the sulfhydryl group of a free cysteine residue. , This approach was used to prepare conjugates of sfGFP with three different proteins: CRISPR-Cas9, a HER2-binding scFv, and nanoluciferase . Further work explored the use of different tyrosinases to expand the scope of tyrosine residues that could be targeted in this manner .…”

Section: Enzymatic Methods and Tag Engineeringmentioning

confidence: 99%

Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

et al. 2022

Self Cite

View full text Add to dashboard Cite

Fusion proteins play an essential role in the biosciences but suffer from several key limitations, including the requirement for N-to-C terminal ligation, incompatibility of constituent domains, incorrect folding, and loss of biological activity. This perspective focuses on chemical and enzymatic approaches for the post-translational generation of well-defined protein−protein conjugates, which overcome some of the limitations faced by traditional fusion techniques. Methods discussed range from chemical modification of nucleophilic canonical amino acid residues to incorporation of unnatural amino acid residues and a range of enzymatic methods, including sortase-mediated ligation. Through summarizing the progress in this rapidly growing field, the key successes and challenges associated with using chemical and enzymatic approaches are highlighted and areas requiring further development are discussed.

show abstract

Section: Enzymatic Methods and Tag Engineeringmentioning

confidence: 99%

Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Examples of this include the attachment of a drug for drug delivery, [6][7][8][9] a fluorophore for visualization [10,11] or a polyethylene glycol (PEG) to improve pharmacokinetics and pharmacodynamics of a protein therapeutic. [12][13][14] Advanced constructs, where a protein is conjugated to another protein [15,16] or oligonucleotides, [17][18][19] have also emerged. This demonstrates the opportunities selective protein conjugation strategies can provide.…”

Section: Introductionmentioning

confidence: 99%

Chemical Conjugation to Less Targeted Proteinogenic Amino Acids

2022

View full text Add to dashboard Cite

Protein bioconjugates are in high demand for applications in biomedicine, diagnostics, chemical biology and bionanotechnology. Proteins are large and sensitive molecules containing multiple different functional groups and in particular nucleophilic groups. In bioconjugation reactions it can therefore be challenging to obtain a homogeneous product in high yield. Numerous strategies for protein conjugation have been developed, of which a vast majority target lysine, cysteine and to a lesser extend tyrosine. Likewise, several methods that involve recombinantly engineered protein tags have been reported. In recent years a number of methods have emerged for chemical bioconjugation to other amino acids and in this review, we present the progress in this area.

show abstract

“…The applications of quinone oxidation have been largely limited to small molecule transformations despite the significant research progress in this area 17,18 . On the other side, in nature, the reactions between oquinones such as DOPA 19 and protein side chains are important but complex in fundamental process of life 20 . Although the early work provided by Mason in 1955 showed that o-quinones could react with proteins via the N-terminal residue 21 , the reaction between o-quinone motifs and proteins have not been fully elucidated on a molecular level 22 .…”

mentioning

confidence: 99%

Modification of N-terminal α-amine of proteins via biomimetic ortho-quinone-mediated oxidation

et al. 2021

View full text Add to dashboard Cite

Naturally abundant quinones are important molecules, which play essential roles in various biological processes due to their reduction potential. In contrast to their universality, the investigation of reactions between quinones and proteins remains sparse. Herein, we report the development of a convenient strategy to protein modification via a biomimetic quinone-mediated oxidation at the N-terminus. By exploiting unique reactivity of an ortho-quinone reagent, the α-amine of protein N-terminus is oxidized to generate aldo or keto handle for orthogonal conjugation. The applications have been demonstrated using a range of proteins, including myoglobin, ubiquitin and small ubiquitin-related modifier 2 (SUMO2). The effect of this method is further highlighted via the preparation of a series of 17 macrophage inflammatory protein 1β (MIP-1β) analogs, followed by preliminary anti-HIV activity and cell viability assays, respectively. This method offers an efficient and complementary approach to existing strategies for N-terminal modification of proteins.

show abstract

Protein–Protein Conjugates: Tyrosine Delivers

Abstract: A tyrosine-targeting bioconjugation reaction leads to a Cas9 protein−peptide conjugate that displays a 20-fold increase in cellular delivery.

Cited by 6 publications

References 10 publications

Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

Chemical Conjugation to Less Targeted Proteinogenic Amino Acids

Modification of N-terminal α-amine of proteins via biomimetic ortho-quinone-mediated oxidation

Contact Info

Product

Resources

About