ArticleProceedings of the National Academy of Sciences of the United States of America2018
Nonproteinogenic deep mutational scanning of linear and cyclic peptides.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Reprogramming FGFR isoform specificity in FGF2 by deep mutational scanning.Chemical science · 2026Article
- Design of peptides with noncanonical amino acids using flow matching.Bioinformatics (Oxford, England) · 2026Article
- Proteome-scale quantification of the interactions driving condensate formation of intrinsically disordered proteins.Nature communications · 2026Article
- Hydrophobic tuning with non-canonical amino acids in a copper metalloenzyme.Nature chemistry · 2026Article
- Direct Selection of Functional De Novo Macrocycles for Activation of On-Cellulo Insulin Receptor.Angewandte Chemie (International ed. in English) · 2026Article
- StrEAMM-Thioether: Efficient Structure Prediction for Thioether-Linked Cyclic Peptides.The journal of physical chemistry. B · 2026Article
- De novo discovery of bicyclic cysteine-rich peptides targeting gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Discovery of Supra-Bivalent GSK3β Inhibitory Peptides Containing an ATP-Mimetic Amino Acid.Journal of the American Chemical Society · 2026Article
- Development of Next Generation Cell-Permeable Peptide Inhibitors for the Oncological Target MAGE-A4.Journal of medicinal chemistry · 2025Article
- Article
- Development of chemokine network inhibitors using combinatorial saturation mutagenesis.Communications biology · 2025Article
- Engineered initiator tRNAs can effectively start translation at non-AUG start codons and diversify N-terminal amino acids for mRNA Display.Nucleic acids research · 2025Article
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation.Nature communications · 2024Article
- Engineering tRNAs for the Ribosomal Translation of Non-proteinogenic Monomers.Chemical reviews · 2024Review
- Cheminformatics-Guided Cell-Free Exploration of Peptide Natural Products.Journal of the American Chemical Society · 2024Article
- Membrane Permeability in a Large Macrocyclic Peptide Driven by a Saddle-Shaped Conformation.Journal of the American Chemical Society · 2024Article
- Drug discovery by targeting the protein-protein interactions involved in autophagy.Acta pharmaceutica Sinica. B · 2023Review
- Discovery and pharmacophoric characterization of chemokine network inhibitors using phage-display, saturation mutagenesis and computational modelling.Nature communications · 2023Article
- A high-throughput microfluidic mechanoporation platform to enable intracellular delivery of cyclic peptides in cell-based assays.Bioengineering & translational medicine · 2023Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-resolution structure-activity analysis of polypeptides requires amino acid structures that are not present in the universal genetic code. Examination of peptide and protein interactions with this resolution has been limited by the need to individually synthesize and test peptides containing nonproteinogenic amino acids. We describe a method to scan entire peptide sequences with multiple nonproteinogenic amino acids and, in parallel, determine the thermodynamics of binding to a partner protein. By coupling genetic code reprogramming to deep mutational scanning, any number of amino acids can be exhaustively substituted into peptides, and single experiments can return all free energy changes of binding. We validate this approach by scanning two model protein-binding peptides with 21 diverse nonproteinogenic amino acids. Dense structure-activity maps were produced at the resolution of single aliphatic atom insertions and deletions. This permits rapid interrogation of interaction interfaces, as well as optimization of affinity, fine-tuning of physical properties, and systematic assessment of nonproteinogenic amino acids in binding and folding.
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