ArticleNature chemical biology2010
Chemoselective small molecules that covalently modify one lysine in a non-enzyme protein in plasma.
Article in Nature chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 89 citations in OpenAlex.
- Computational Design of Lysine Targeting Covalent Binders Using Rosetta.Journal of chemical information and modeling · 2025Article
- The conformational landscape of human transthyretin revealed by cryo-EM.Nature structural & molecular biology · 2025Article
- Development and preclinical testing of a naloxone prodrug depot for extended protection against opioid overdose.Nature communications · 2025Article
- Prolonged Activation of the GLP-1 Receptor via Covalent Capture.ACS chemical biology · 2024Article
- A pyridinium-based strategy for lysine-selective protein modification and chemoproteomic profiling in live cells.Chemical science · 2024Article
- The conformational landscape of human transthyretin revealed by cryo-EM.bioRxiv : the preprint server for biology · 2024Article
- Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase.Chembiochem : a European journal of chemical biology · 2023Article
- Peripherally restricted transthyretin-based delivery system for probes and therapeutics avoiding opioid-related side effects.Nature communications · 2022Article
- Functionalized quinolizinium-based fluorescent reagents for modification of cysteine-containing peptides and proteins.RSC advances · 2022Article
- A proteome-wide atlas of lysine-reactive chemistry.Nature chemistry · 2021Article
- Recent developments in chemical conjugation strategies targeting native amino acids in proteins and their applications in antibody-drug conjugates.Chemical science · 2021Review
- Enhancing the Pharmacokinetic Profile of Interleukin 2 through Site-Specific Conjugation to a Selective Small-Molecule Transthyretin Ligand.Journal of medicinal chemistry · 2021Article
- Precision Modification of Native Antibodies.Bioconjugate chemistry · 2021Review
- Visualizing and trapping transient oligomers in amyloid assembly pathways.Biophysical chemistry · 2021Review
- The design and development of covalent protein-protein interaction inhibitors for cancer treatment.Journal of hematology & oncology · 2020Review
- Review on the Structures and Activities of Transthyretin Amyloidogenesis Inhibitors.Drug design, development and therapy · 2020Review
- Recent Advances in Selective and Irreversible Covalent Ligand Development and Validation.Cell chemical biology · 2019Review
- Hydrophilic Small Molecules That Harness Transthyretin To Enhance the Safety and Efficacy of Targeted Chemotherapeutic Agents.Molecular pharmaceutics · 2019Article
- A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity.Chemical science · 2019Article
- Peptide-Based Inhibitors of Fimbrial Biogenesis in Porphyromonas gingivalis.Infection and immunity · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
A small molecule that could bind selectively to and then react chemoselectively with a non-enzyme protein in a complex biological fluid, such as blood, could have numerous practical applications. Herein, we report a family of designed stilbenes that selectively and covalently modify the prominent plasma protein transthyretin in preference to more than 4,000 other human plasma proteins. They react chemoselectively with only one of eight lysine e-amino groups within transthyretin. The crystal structure confirms the expected binding orientation of the stilbene substructure and the anticipated conjugating amide bond. These covalent transthyretin kinetic stabilizers exhibit superior amyloid inhibition potency compared to their noncovalent counterparts, and they prevent cytotoxicity associated with amyloidogenesis. Though there are a few prodrugs that, upon metabolic activation, react with a cysteine residue inactivating a specific non-enzyme, we are unaware of designed small molecules that react with one lysine e-amine within a specific non-enzyme protein in a complex biological fluid.
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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.