ArticleBioconjugate chemistry2013
A highly efficient catalyst for oxime ligation and hydrazone-oxime exchange suitable for bioconjugation.
Article in Bioconjugate chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 112 citations in OpenAlex.
- Strategic and Chemical Advances in Antibody-Drug Conjugates.Pharmaceutics · 2025Review
- Engineering protein prenylation: an emerging tool for selective protein modification.Biochemical Society transactions · 2025Review
- Enzymatic Construction of DARPin-Based Targeted Delivery Systems Using Protein Farnesyltransferase and a Capture and Release Strategy.International journal of molecular sciences · 2022Article
- Expanding the versatility and scope of the oxime ligation: rapid bioconjugation to disulfide-rich peptides.Chemical communications (Cambridge, England) · 2022Article
- 6″-Modifed α-GalCer-peptide conjugate vaccine candidates protect against liver-stage malaria.RSC chemical biology · 2022Article
- A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications.Chemical reviews · 2021Review
- Advances in Cryochemistry: Mechanisms, Reactions and Applications.Molecules (Basel, Switzerland) · 2021Review
- One-pot oxime ligation from peptides bearing thiazolidine and aminooxyacetyl groups.RSC advances · 2020Article
- Ketoxime peptide ligations: oxidative couplings of alkoxyamines toChemical science · 2019Article
- Multiple adaptation of constitutional dynamic networks and information storage in constitutional distributions of acylhydrazones.Chemical science · 2019Article
- Recent progress in enzymatic protein labelling techniques and their applications.Chemical Society reviews · 2018Review
- Hydrolytic Decomposition of S-Aroylthiooximes: Effect of pH and N-Arylidene Substitution on Reaction Rate.The Journal of organic chemistry · 2018Article
- Exceptionally rapid oxime and hydrazone formation promoted by catalytic amine buffers with low toxicity.Chemical science · 2018Article
- Generation of Dynamic Combinatorial Libraries Using Hydrazone-Functionalized Surface Mimetics.European journal of organic chemistry · 2018Article
- Saline Accelerates Oxime Reaction with Aldehyde and Keto Substrates at Physiological pH.Scientific reports · 2018Article
- Borylated oximes: versatile building blocks for organic synthesis.Chemical communications (Cambridge, England) · 2017Article
- Oximes and Hydrazones in Bioconjugation: Mechanism and Catalysis.Chemical reviews · 2017Review
- Targeting Reactive Carbonyls for Identifying Natural Products and Their Biosynthetic Origins.Journal of the American Chemical Society · 2016Article
- The third orthogonal dynamic covalent bond.Chemical science · 2016Article
- Site-Specific PEGylation of Therapeutic Proteins.International journal of molecular sciences · 2015Review
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6 authors at 1 institution in 1 country.
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Abstract
Imine-based reactions are useful for a wide range of bioconjugation applications. Although aniline is known to catalyze the oxime ligation reaction under physiological conditions, it suffers from slow reaction kinetics, specifically when a ketone is being used or when hydrazone-oxime exchange is performed. Here, we report on the discovery of a new catalyst that is up to 15 times more efficient than aniline. That catalyst, m-phenylenediamine (mPDA), was initially used to analyze the kinetics of oxime ligation on aldehyde- and ketone-containing small molecules. While mPDA is only modestly more effective than aniline when used in equal concentrations (~2-fold), its much greater aqueous solubility relative to aniline allows it to be used at higher concentrations, resulting in significantly more efficient catalysis. In the context of protein labeling, it was first used to site-specifically label an aldehyde-functionalized protein through oxime ligation, and its kinetics were compared to reaction with aniline. Next, a protein was labeled with an aldehyde-containing substrate in crude cell lysate, captured with hydrazide-functionalized beads and then the kinetics of immobilized protein release via hydrazone-oxime exchange were analyzed. Our results show that mPDA can release and label 15 times more protein than aniline can in 3 h. Then, using the new catalyst, ciliary neurotrophic factor, a protein with therapeutic potential, was successfully labeled with a fluorophore in only 5 min. Finally, a protein containing the unnatural amino acid, p-acetyl phenylalanine, a ketone-containing residue, was prepared and PEGylated efficiently via oxime ligation using mPDA. This new catalyst should have a significant impact on the field of bioconjugation, where oxime ligation and hydrazone-oxime exchange are commonly employed.
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