ArticleNature chemistry2019
Maleimide-thiol adducts stabilized through stretching.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
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- The nucleic acid reactions on the nanomaterials surface for biomedicine.Journal of nanobiotechnology · 2025Review
- Diverse reactivity of maleimides in polymer science and beyond.Polymer international · 2025Article
- Bio-orthogonal tuning of matrix properties during 3D cell culture to induce morphological and phenotypic changes.Nature protocols · 2025Review
- Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.Acta pharmaceutica Sinica. B · 2025Article
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- Evolution of Pyrrolysyl-tRNA Synthetase: From Methanogenesis to Genetic Code Expansion.Chemical reviews · 2024Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Maleimide-thiol reactions are widely used to produce protein-polymer conjugates for therapeutics. However, maleimide-thiol adducts are unstable in vivo or in the presence of thiol-containing compounds because of the elimination of the thiosuccinimide linkage through a retro-Michael reaction or thiol exchange. Here, using single-molecule force spectroscopy, we show that applying an appropriate stretching force to the thiosuccinimide linkage can considerably stabilize the maleimide-thiol adducts, in effect using conventional mechanochemistry of force-accelerated bond dissociation to unconventionally stabilize an adjacent bond. Single-molecule kinetic analysis and bulk structural characterizations suggest that hydrolysis of the succinimide ring is dominant over the retro-Michael reaction through a force-dependent kinetic control mechanism, and this leads to a product that is resistant to elimination. This unconventional mechanochemical approach enabled us to produce stable polymer-protein conjugates by simply applying a mechanical force to the maleimide-thiol adducts through mild ultrasonication. Our results demonstrate the great potential of mechanical force for stimulating important productive chemical transformations.
Identifiers
30718898What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.