ArticleACS central science2023
Comprehensive Structure-Activity Relationship Studies of Cepafungin Enabled by Biocatalytic C-H Oxidations.
Article in ACS central science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Lipopeptide Engineering: From Natural Origins to Rational Design Against Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2026Review
- Exploring the Synthetic Potential of Horner-Wadsworth-Emmons Reaction Toward the Synthesis of Polyketide Based Natural Products: A Review.Topics in current chemistry (Cham) · 2025Review
- Computational analysis of antimicrobial peptides targeting key receptors in infection-related cardiovascular diseases: molecular docking and dynamics insights.Scientific reports · 2025Article
- Enantioselective total synthesis of lycoposerramine congeners through late-stage nitrogen deletion.Nature communications · 2025Article
- Sequential oxidation of L-lysine by a non-heme iron hydroxylase.bioRxiv : the preprint server for biology · 2025Article
- Organic Synthesis and Catalysis Enable Facile Access to Bioactive Compounds and Drugs.ACS central science · 2025Article
- Biocatalytic C-H oxidation meets radical cross-coupling: Simplifying complex piperidine synthesis.Science (New York, N.Y.) · 2024Article
- Advances, opportunities, and challenges in methods for interrogating the structure activity relationships of natural products.Natural product reports · 2024Review
- Optical Control of Proteasomal Protein Degradation with a Photoswitchable Lipopeptide.Angewandte Chemie (International ed. in English) · 2024Article
- Multiplexed Assessment of Promiscuous Non-Canonical Amino Acid Synthase Activity in a Pyridoxal Phosphate-Dependent Protein Family.ACS catalysis · 2023Article
- Non-Native Site-Selective Enzyme Catalysis.Chemical reviews · 2023Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The cepafungins are a class of highly potent and selective eukaryotic proteasome inhibitor natural products with potential to treat refractory multiple myeloma and other cancers. The structure-activity relationship of the cepafungins is not fully understood. This Article chronicles the development of a chemoenzymatic approach to cepafungin I. A failed initial route involving derivatization of pipecolic acid prompted us to examine the biosynthetic pathway for the production of 4-hydroxylysine, which culminated in the development of a 9-step synthesis of cepafungin I. An alkyne-tagged analogue enabled chemoproteomic studies of cepafungin and comparison of its effects on global protein expression in human multiple myeloma cells to the clinical drug bortezomib. A preliminary series of analogues elucidated critical determinants of potency in proteasome inhibition. Herein we report the chemoenzymatic syntheses of 13 additional analogues of cepafungin I guided by a proteasome-bound crystal structure, 5 of which are more potent than the natural product. The lead analogue was found to have 7-fold greater proteasome β5 subunit inhibitory activity and has been evaluated against several multiple myeloma and mantle cell lymphoma cell lines in comparison to the clinical drug bortezomib.
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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.