ArticleScientific reports2016
Cellular uptake of a cystine-knot peptide and modulation of its intracellular trafficking.
Article in Scientific reports, 2016. 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, 29 citations in OpenAlex.
- Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues.ACS bio & med chem Au · 2024Article
- Cystine-knot peptide inhibitors of HTRA1 bind to a cryptic pocket within the active site region.Nature communications · 2024Article
- A phage-displayed disulfide constrained peptide discovery platform yields novel human plasma protein binders.PloS one · 2024Article
- Discovery and Characterization of MaK: A Novel Knottin Antimicrobial Peptide fromInternational journal of molecular sciences · 2023Article
- Effect of the Peptide Calcium Channel Blocker ω-hexatoxin-Hv1a on Cell Death during Ischemia/ReperfusionSovremennye tekhnologii v meditsine · 2023Article
- Fatty acylation enhances the cellular internalization and cytosolic distribution of a cystine-knot peptide.iScience · 2021Article
- Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides.ACS chemical biology · 2021Article
- Scalable Biosynthetic Production of Knotted Peptides Enables ADME and Thermodynamic Folding Studies.ACS omega · 2021Article
- Nanolipoprotein particles for co-delivery of cystine-knot peptides and Fab-based therapeutics.Nanoscale advances · 2021Article
- Roseltide rT7 is a disulfide-rich, anionic, and cell-penetrating peptide that inhibits proteasomal degradation.The Journal of biological chemistry · 2019Article
- Visualizing the cellular route of entry of a cystine-knot peptide with Xfect transfection reagent by electron microscopy.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclotides or cyclic cystine-knot peptides have emerged as a promising class of pharmacological ligands that modulate protein function. Interestingly, very few cyclotides have been shown to enter into cells. Yet, it remains unknown whether backbone cyclization is required for their cellular internalization. In this report, we studied the cellular behavior of EETI-II, a model acyclic cystine-knot peptide. Even though synthetic methods have been used to generate EETI-II, recombinant methods that allow efficient large scale biosynthesis of EETI-II have been lagging. Here, we describe a novel protocol for recombinant generation of folded EETI-II in high yields and to near homogeneity. We also uncover that EETI-II is efficiently uptaken via an active endocytic pathway to early endosomes in mammalian cells, eventually accumulating in late endosomes and lysosomes. Notably, co-incubation with a cell-penetrating peptide enhanced the cellular uptake and altered the trafficking of EETI-II, leading to its evasion of lysosomes. Our results demonstrate the feasibility of modulating the subcellular distribution and intracellular targeting of cystine-knot peptides, and hence enable future exploration of their utility in drug discovery and delivery.
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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.