Anchor extension: a structure-guided approach to design cyclic peptides targeting enzyme active sites.
Catalytic Domain
/ drug effects
Crystallography, X-Ray
Drug Design
Enzyme Assays
Histone Deacetylase 2
/ antagonists & inhibitors
Histone Deacetylase 6
/ antagonists & inhibitors
Histone Deacetylase Inhibitors
/ chemistry
Inhibitory Concentration 50
Molecular Docking Simulation
Nuclear Magnetic Resonance, Biomolecular
Peptide Library
Peptides, Cyclic
/ chemistry
Recombinant Proteins
/ genetics
Structure-Activity Relationship
Zebrafish Proteins
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 06 2021
07 06 2021
Historique:
received:
09
06
2020
accepted:
04
05
2021
entrez:
8
6
2021
pubmed:
9
6
2021
medline:
16
6
2021
Statut:
epublish
Résumé
Despite recent success in computational design of structured cyclic peptides, de novo design of cyclic peptides that bind to any protein functional site remains difficult. To address this challenge, we develop a computational "anchor extension" methodology for targeting protein interfaces by extending a peptide chain around a non-canonical amino acid residue anchor. To test our approach using a well characterized model system, we design cyclic peptides that inhibit histone deacetylases 2 and 6 (HDAC2 and HDAC6) with enhanced potency compared to the original anchor (IC
Identifiants
pubmed: 34099674
doi: 10.1038/s41467-021-23609-8
pii: 10.1038/s41467-021-23609-8
pmc: PMC8185074
doi:
Substances chimiques
Histone Deacetylase Inhibitors
0
Peptide Library
0
Peptides, Cyclic
0
Recombinant Proteins
0
Zebrafish Proteins
0
HDAC2 protein, human
EC 3.5.1.98
HDAC6 protein, human
EC 3.5.1.98
HDAC6 protein, zebrafish
EC 3.5.1.98
Histone Deacetylase 2
EC 3.5.1.98
Histone Deacetylase 6
EC 3.5.1.98
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3384Subventions
Organisme : NIGMS NIH HHS
ID : F32 GM120791
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM049758
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122543
Pays : United States
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