ArticleACS chemical biology2015
Peptide library approach to uncover phosphomimetic inhibitors of the BRCA1 C-terminal domain.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.Signal transduction and targeted therapy · 2024Review
- Using AI-predicted protein structures as a reference to predict loss-of-function activity in tumor suppressor breast cancer genes.Computational and structural biotechnology journal · 2024Article
- Reaching New Heights in Genetic Code Manipulation with High Throughput Screening.Chemical reviews · 2024Review
- Peptide-Based Agents for Cancer Treatment: Current Applications and Future Directions.International journal of molecular sciences · 2023Review
- Development of a Cyclic, Cell Penetrating Peptide Compatible with In Vitro Selection Strategies.ACS chemical biology · 2023Article
- Regulation of DNA damage response by trimeric G-proteins.iScience · 2023Article
- Anti-cancer peptide-based therapeutic strategies in solid tumors.Cellular & molecular biology letters · 2022Article
- Non-canonical Amino Acid Substrates of E. coli Aminoacyl-tRNA Synthetases.Chembiochem : a European journal of chemical biology · 2022Review
- MOrPH-PhD: A Phage Display System for the Functional Selection of Genetically Encoded Macrocyclic Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Discovery and Validation of Lmj_04_BRCT Domain, a Novel Therapeutic Target: Identification of Candidate Drugs for Leishmaniasis.International journal of molecular sciences · 2021Article
- Biosynthetic Strategies for Macrocyclic Peptides.Molecules (Basel, Switzerland) · 2021Review
- Expanding the Chemical Diversity of Genetically Encoded Libraries.ACS combinatorial science · 2020Article
- Expanded toolbox for directing the biosynthesis of macrocyclic peptides in bacterial cells.Chemical science · 2020Article
- Direct, Competitive Comparison of Linear, Monocyclic, and Bicyclic Libraries Using mRNA Display.ACS combinatorial science · 2020Article
- MOrPH-PhD: An Integrated Phage Display Platform for the Discovery of Functional Genetically Encoded Peptide Macrocycles.ACS central science · 2020Article
- Review
- Fanconi anemia pathway as a prospective target for cancer intervention.Cell & bioscience · 2020Review
- A new strategy for the in vitro selection of stapled peptide inhibitors by mRNA display.Chemical communications (Cambridge, England) · 2019Article
- In vitro genetic code reprogramming and expansion to study protein function and discover macrocyclic peptide ligands.Current opinion in chemical biology · 2018Review
- Highly Constrained Bicyclic Scaffolds for the Discovery of Protease-Stable Peptides via mRNA Display.ACS chemical biology · 2017Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Many intracellular protein-protein interactions are mediated by the phosphorylation of serine, and phosphoserine-containing peptides can inhibit these interactions. However, hydrolysis of the phosphate by phosphatases, and the poor cell permeability associated with phosphorylated peptides has limited their utility in cellular and in vivo contexts. Compounding the problem, strategies to replace phosphoserine in peptide inhibitors with easily accessible mimetics (such as Glu or Asp) routinely fail. Here, we present an in vitro selection strategy for replacement of phosphoserine. Using mRNA display, we created a 10 trillion member structurally diverse unnatural peptide library. From this library, we found a peptide that specifically binds to the C-terminal domain (BRCT)2 of breast cancer associated protein 1 (BRCA1) with an affinity comparable to phosphorylated peptides. A crystal structure of the peptide bound reveals that the pSer-x-x-Phe motif normally found in BRCA1 (BRCT)2 binding partners is replaced by a Glu-x-x-4-fluoroPhe and that the peptide picks up additional contacts on the protein surface not observed in cognate phosphopeptide binding. Expression of the peptide in human cells led to defects in DNA repair by homologous recombination, a process BRCA1 is known to coordinate. Overall, this work validates a new in vitro selection approach for the development of inhibitors of protein-protein interactions mediated by serine phosphorylation.
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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.