The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index.
Tethering: Fragment-Based Drug Discovery
Abstract
▪ Abstract The genomics revolution has provided a deluge of new targets for drug discovery. To facilitate the drug discovery process, many researchers are turning to fragment-based approaches to find lead molecules more efficiently. One such method, Tethering 1 , allows for the identification of small-molecule fragments that bind to specific regions of a protein target. These fragments can then be elaborated, combined with other molecules, or combined with one another to provide high-affinity drug leads. In this review we describe the background and theory behind Tethering and discuss its use in identifying novel inhibitors for protein targets including interleukin-2 (IL-2), thymidylate synthase (TS), protein tyrosine phosphatase 1B (PTP-1B), and caspases.
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“The inhibitor (compound 12 in their study) was discovered through a disulfide-fragment screening approach known as tethering, whereby a library of 480 disulfide fragments was screened against KRAS(G12C) in the GDP-bound state using intact protein mass spectrometry (MS)88,90.”
From Advances in covalent drug discovery (2022) · cites this paper as [90]
In the citing paper
“Originally, MS-based compound screening grew out of ‘tethering’, which is a technique employed since 2000 that uses libraries of compounds linked to disulfides to identify fragments that bind cysteine-adjacent pockets90,147.”
From Advances in covalent drug discovery (2022) · cites this paper as [90]
Citations
Cites
A Combinatorial Approach Defines Specificities of Members of the Caspase Family and Granzyme B
Thornberry, N. A., Rano, T. A., Peterson, E. P., Rasper, D., Timkey, T., Garcia-Calvo, M. M., Houtzager, V. M., Nordstrom, P. A., Roy, S., Vaillancourt, J. P., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.29.17907 · Cited by 2,089
Discovering High-Affinity Ligands for Proteins: SAR by NMR
Shuker, S. B., Hajduk, P. J., Meadows, R. P., & Fesik, S. W. (1996) · Science · doi:10.1126/science.274.5292.1531 · Cited by 2,045
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Schindler, T. H., Bornmann, W. G., Pellicena, P., Miller, W. T., Clarkson, B., & Kuriyan, J. (2000) · Science · doi:10.1126/science.289.5486.1938 · Cited by 1,785
The Conformational Plasticity of Protein Kinases
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Powers, J. C., Asgian, J. L., Ekici, Ö. D., & James, K. E. (2002) · Chemical Reviews · doi:10.1021/cr010182v · Cited by 1,090 · cited 1×
“These include proteases (27, 29, 30, 57, 59, 63), kinases (24, 74), and phosphatases (4, 28, 50), all classes of enzymes that are heavily pursued in the pharmaceutical industry.”
BackgroundA Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening
McGovern, S. L., Caselli, E., Grigorieff, N., & Shoichet, B. K. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm010533y · Cited by 1,048
Inhibition of Human Caspases by Peptide-based and Macromolecular Inhibitors
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On the attribution and additivity of binding energies
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Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site
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Research works printed but not linked: 1
- Graczyk PP, 1999, Restor. Neurol. Neurosci., 14, 1
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Structure-function studies of glutaredoxins and related oxidoreductases
Elgán, T. H. (2008) · Figshare
Metadata
- Authors
- Erlanson, D. A., Wells, J. A., & Braisted, A. C.
- Affiliations
- Sunesis (United States) (US)
- Venue
- Annual Review of Biophysics and Biomolecular Structure
- Publisher
- Annual Reviews
- Published
- 2004-06-09
- Volume
- 33
- Issue
- 1
- Pages
- 199-223
- ISSN
- 1056-8700 (ISSN-L)
- 1545-4266
- OpenAlex
- W2138958920
- Cited by
- 385
- References
- 78
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 17 · 2023: 16 · 2022: 17 · 2021: 8 · 2020: 17 · 2019: 17 · 2018: 21 · 2017: 6 · 2016: 18 · 2015: 21 · 2014: 23 · 2013: 11 · 2012: 29
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biophysics and Biomolecular Structure (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sunesis
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
- Keywords
- tethering, fragment-based drug discovery, small-molecule fragments, protein-ligand binding, lead compound identification, interleukin-2, thymidylate synthase, PTP1B, caspases, protein inhibitors
- MeSH terms
- Binding Sites, Peptide Fragments, Protein Binding, Proteins, Drug Design, Protein Interaction Mapping, Protein Array Analysis
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