ArticleBioconjugate chemistry2011
Tunable degradation of maleimide-thiol adducts in reducing environments.
Article in Bioconjugate chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 1 of them a synthesis that pooled it.
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Who cites it
168 citing papers in PubMed, 1 synthesis or guideline pooled it, 443 citations in OpenAlex.
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- A Chemical Framework for Engineering Extracellular Vesicles' Biointerface to Advance Precision Therapeutics.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Genetic Code Expansion Enables Oriented, Site-Specific Conjugation of DARPins to Lipid Nanoparticles for Selective mRNA Delivery to CD8International journal of molecular sciences · 2026Article
- Microscale Mechanical Cues in Hydrogels: Engineering Strategies to Modulate Cell Fates in Three Dimensions.Cell biomaterials · 2026Article
- On-resin assembly of cysteine-reactive linkers for controlled site-selective antibody bioconjugation.Nature protocols · 2026Review
- Spontaneous Non-Catalyzed Molecular Reactions and Interactions in the Human Body: Biomedical Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Six-Fold Methyl Internal Rotation andThe journal of physical chemistry. A · 2026Article
- Development of a Self-Adjuvanting Influenza Peptide-Glycolipid Conjugate Inducing CD8Chembiochem : a European journal of chemical biology · 2026Article
- Traceless linkers used for reversible protein-polymer conjugations.Chemical science · 2026Review
- Tunable Linkers for Dynamic Thiol-Based Bioconjugation Strategies.Biomacromolecules · 2026Review
- Cross-Linking PEG Microgels with Mesoporous Organosilica Nanoparticles to Engineer Microporous Annealed Particle Scaffold Properties.ACS omega · 2026Article
- Integrating In Vitro Analytics for Improved Antibody-Drug Conjugate Candidate Selection.Cancers · 2026Article
- Structural Characterization of Linker Shielding in ADC Site-Specific Conjugates.Pharmaceutics · 2025Article
- Site-specific PEGylation of proteins: Insights into structural and functional changes.Acta pharmaceutica Sinica. B · 2025Review
- Identification of a Novel Linker Enabling the Bioconjugation of a Cyclic Dinucleotide for the STING Antibody-Drug Conjugate TAK-500.Bioconjugate chemistry · 2025Article
- A Comparative Study on the Effect of Near-Infrared Fluorescent Dyes on the Pharmacokinetic Behavior of Nanobody-Based Tracers for In Vivo Imaging.Journal of medicinal chemistry · 2025Article
- Profiling the landscape of cysteine posttranslational modifications in brain aging and neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Mass spectrometric imaging and quantitative analysis of theInorganic chemistry frontiers · 2025Article
108 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Addition chemistries are widely used in preparing biological conjugates, and in particular, maleimide-thiol adducts have been widely employed. Here, we show that the resulting succinimide thioether formed by the Michael-type addition of thiols to N-ethylmaleimide (NEM), generally accepted as stable, undergoes retro and exchange reactions in the presence of other thiol compounds at physiological pH and temperature, offering a novel strategy for controlled release. Model studies ((1)H NMR, HPLC) of NEM conjugated to 4-mercaptophenylacetic acid (MPA), N-acetylcysteine, or 3-mercaptopropionic acid (MP) incubated with glutathione showed half-lives of conversion from 20 to 80 h, with extents of conversion from 20% to 90% for MPA and N-acetylcysteine conjugates. After ring-opening, the resultant succinimide thioether did not show retro and exchange reactions. The kinetics of the retro reactions and extent of exchange can be modulated by the Michael donor's reactivity; therefore, the degradation of maleimide-thiol adducts could be tuned for controlled release of drugs or degradation of materials at time scales different than those currently possible via disulfide-mediated release. Such approaches may find a new niche for controlled release in reducing environments relevant in chemotherapy and subcellular trafficking.
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