The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
How proteins bind macrocycles
Open accessAbstract
The potential utility of synthetic macrocycles as drugs, particularly against low druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of macrocycles for good target protein-binding activity or bioavailability. To address this knowledge gap we analyze the binding modes of a representative set of macrocycle-protein complexes. The results, combined with consideration of the physicochemical properties of approved macrocyclic drugs, allow us to propose specific guidelines for the design of synthetic macrocycles libraries possessing structural and physicochemical features likely to favor strong binding to protein targets and also good bioavailability. We additionally provide evidence that large, natural product derived macrocycles can bind to targets that are not druggable by conventional, drug-like compounds, supporting the notion that natural product inspired synthetic macrocycles can expand the number of proteins that are druggable by synthetic small molecules.
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Cites
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Self-citation
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Metadata
- Authors
- Villar, E. A., Beglov, D., Chennamadhavuni, S., Porco, J. A., Kozakov, D., Vajda, S., & Whitty, A.
- Venue
- Nature Chemical Biology
- Published
- 2014-07-20
- Volume
- 10
- Issue
- 9
- Pages
- 723-731
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W2091492589
- Cited by
- 400
- References
- 54
- FWCI
- 13.26
- Type
- journal article
- Language
- en
- Open access
- green
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- Villar, E. A., Beglov, D., Chennamadhavuni, S., Porco, J. A., Kozakov, D., Vajda, S., & Whitty, A. (2014). How proteins bind macrocycles. Nature Chemical Biology. https://doi.org/10.1038/nchembio.1584
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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