ArticleRSC chemical biology2024
Chemical synthesis of grafted cyclotides using a "plug and play" approach.
Article in RSC chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Computational screening of Viola odorata cyclotides identifies Phyb C as potential PD-1 inhibitor for cancer immunotherapy.Molecular diversity · 2026Article
- Cyclic Peptides as Modulators of Protein-Protein Interactions: A Survival Guide from Discovery Platforms to AI-Driven Design.International journal of molecular sciences · 2026Review
- Cyclotides from Plants Driving the Next Generation of Antibacterial Agents.Antibiotics (Basel, Switzerland) · 2026Review
- Plant Peptides on the Rise: From Historical Insight to Future Applications.Plant biotechnology journal · 2026Review
- Computational screening of AI-derived cyclotides as putative VEGFR2 binders for wound-site angiogenesis.Scientific reports · 2026Article
- The rise and future of peptide-based antimicrobials.Journal of microbiology (Seoul, Korea) · 2026Review
- Engineering Peptide Modulators for T-Cell Migration by Structural Scaffold Matching.Journal of medicinal chemistry · 2025Article
- Small and Versatile Cyclotides as Anti-infective Agents.ACS infectious diseases · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Cyclotides are a diverse class of plant-derived cyclic, disulfide-rich peptides with a unique cyclic cystine knot topology. Their remarkable structural stability and resistance to proteolytic degradation can lead to improved pharmacokinetics and oral activity as well as selectivity and high enzymatic stability. Thus, cyclotides have emerged as powerful scaffold molecules for designing peptide-based therapeutics. The chemical engineering of cyclotides has generated novel peptide ligands of G protein-coupled receptors (GPCRs), today's most exploited drug targets. However key challenges potentially limit the widespread use of cyclotides in molecular grafting applications. Folding of cyclotides containing bioactive epitopes remains a major bottleneck in cyclotide synthesis. Here we present a modular 'plug and play' approach that effectively bypasses problems associated with the oxidative folding of cyclotides. By grafting onto a pre-formed acyclic cyclotide-like scaffold we show that difficult-to-graft sequences can be easily obtained and can target GPCRs with nanomolar affinities and potencies. We further show the suitability of this new method to graft other complex epitopes including structures with additional disulfide bonds that are not readily available
Identifiers
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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.