Nature Communications (Jun 2021)
Anchor extension: a structure-guided approach to design cyclic peptides targeting enzyme active sites
- Parisa Hosseinzadeh,
- Paris R. Watson,
- Timothy W. Craven,
- Xinting Li,
- Stephen Rettie,
- Fátima Pardo-Avila,
- Asim K. Bera,
- Vikram Khipple Mulligan,
- Peilong Lu,
- Alexander S. Ford,
- Brian D. Weitzner,
- Lance J. Stewart,
- Adam P. Moyer,
- Maddalena Di Piazza,
- Joshua G. Whalen,
- Per Jr. Greisen,
- David W. Christianson,
- David Baker
Affiliations
- Parisa Hosseinzadeh
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Paris R. Watson
- Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania
- Timothy W. Craven
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Xinting Li
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Stephen Rettie
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Fátima Pardo-Avila
- Department of Structural Biology, Stanford University School of Medicine
- Asim K. Bera
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Vikram Khipple Mulligan
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Peilong Lu
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Alexander S. Ford
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Brian D. Weitzner
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Lance J. Stewart
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Adam P. Moyer
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Maddalena Di Piazza
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Joshua G. Whalen
- University of Washington, Department of Biochemistry, Institute for Protein Design
- Per Jr. Greisen
- University of Washington, Department of Biochemistry, Institute for Protein Design
- David W. Christianson
- Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania
- David Baker
- University of Washington, Department of Biochemistry, Institute for Protein Design
- DOI
- https://doi.org/10.1038/s41467-021-23609-8
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 12
Abstract
Cyclic peptides are of particular interest due to their pharmacological properties, but their design for binding to a target protein is challenging. Here, the authors present a computational “anchor extension” methodology for de novo design of cyclic peptides that bind to the target protein with high affinity, and validate the approach by developing cyclic peptides that inhibit histone deacetylases 2 and 6.
