ArticleJournal of medicinal chemistry2019
Protein Stability Effects in Aggregate-Based Enzyme Inhibition.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Design, Synthesis, and Evaluation of Selective Ubiquitin-Specific Protease 11 (USP11) Inhibitors.ACS omega · 2025Article
- Colloidal Aggregation Confounds Cell-Based Covid-19 Antiviral Screens.Journal of medicinal chemistry · 2024Article
- Nanomolar Protein Thermal Profiling with Modified Cyanine Dyes.Analytical chemistry · 2023Article
- The potential use of glycosyl-transferase inhibitors for targeted reduction of S. mutans biofilms in dental materials.Scientific reports · 2023Article
- Efflux Pump-Binding 4(3-Aminocyclobutyl)Pyrimidin-2-Amines Are Colloidal Aggregators.Biomolecules · 2023Article
- Characterizing inhibitors of human AP endonuclease 1.PloS one · 2023Article
- Controlling amyloid formation of intrinsically disordered proteins and peptides: slowing down or speeding up?Essays in biochemistry · 2022Article
- Destabilization of the SHP2 and SHP1 protein tyrosine phosphatase domains by a non-conserved "backdoor" cysteine.Biochemistry and biophysics reports · 2022Article
- Xenopus laevis and human type 3 iodothyronine deiodinase enzyme cross-species sensitivity to inhibition by ToxCast chemicals.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
- A rebinding-assay for measuring extreme kinetics using label-free biosensors.Scientific reports · 2021Article
- A Crowding Barrier to Protein Inhibition in Colloidal Aggregates.Journal of medicinal chemistry · 2021Article
- Targeting a Pathogenic Cysteine Mutation: Discovery of a Specific Inhibitor of Y279C SHP2.Biochemistry · 2020Article
- Unlocking latent kinetic information from label-free binding.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Small-molecule aggregates are a leading cause of artifacts in early drug discovery, but little is known about their interactions with proteins, nor why some proteins are more susceptible to inhibition than others. A possible reason for this apparent selectivity is that aggregation-based inhibition, as a stoichiometric process, is sensitive to protein concentration, which varies across assays. Alternatively, local protein unfolding by aggregates may lead to selectivity since stability varies among proteins. To deconvolute these effects, we used differentially stable point mutants of a single protein, TEM-1 β-lactamase. Broadly, destabilized mutants had higher affinities for and were more potently inhibited by aggregates versus more stable variants. The addition of the irreversible inhibitor moxalactam destabilized several mutants, and these typically bound tighter to a colloidal particle, while the only mutant it stabilized bound weaker. These results suggest that less-stable enzymes are more easily sequestered and inhibited by colloidal aggregates.
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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.