ArticleNature chemistry2014
Synthetic fermentation of bioactive non-ribosomal peptides without organisms, enzymes or reagents.
Article in Nature chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 28 citations in OpenAlex.
- Predicting three-component reaction outcomes from ~40,000 miniaturized reactant combinations.Science advances · 2025Article
- Activity-Directed Synthesis: A Flexible Approach for Lead Generation.ChemMedChem · 2020Article
- Activity-Directed Synthesis of Inhibitors of the p53/hDM2 Protein-Protein Interaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Synthetic fermentation of β-peptide macrocycles by thiadiazole-forming ring-closing reactions.Chemical science · 2018Article
- Combinatorial chemistry in drug discovery.Current opinion in chemical biology · 2017Review
- Activity-Directed Synthesis with Intermolecular Reactions: Development of a Fragment into a Range of Androgen Receptor Agonists.Angewandte Chemie (International ed. in English) · 2015Article
- Drug discovery: Combichem all over again.Nature chemistry · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microbial fermentation can rapidly provide potent compounds that can be easily screened for biological activity, and the active components can be isolated. Its success in drug discovery has inspired extensive efforts to modulate and control the products. In this Article, we document a 'synthetic fermentation' of bioactive, unnatural peptides 'grown' from small building blocks in water using amide-forming ligations. No organisms, enzymes or reagents are needed. The sequences, structures and compositions of the products can be modulated by adjusting the building blocks and conditions. No specialized knowledge of organic chemistry or handling of toxic material is required to produce complex organic molecules. The 'fermentations' can be conducted in arrays and screened for biological activity without isolation or workup. As a proof-of-concept, about 6,000 unnatural peptides were produced from just 23 building blocks, from which a hepatitis C virus NS3/4A protease inhibitor with a half-maximum inhibitory concentration of 1.0 μM was identified and characterized.
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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.