ArticleiScience2021
Fatty acylation enhances the cellular internalization and cytosolic distribution of a cystine-knot peptide.
Article in iScience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 10 citations in OpenAlex.
- Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.Chemical reviews · 2025Review
- Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity.Molecular cancer therapeutics · 2024Article
- Bioproduction Platform to Generate Functionalized Disulfide-Constrained Peptide Analogues.ACS bio & med chem Au · 2024Article
- A phage-displayed disulfide constrained peptide discovery platform yields novel human plasma protein binders.PloS one · 2024Article
- Development of a New Class of CXCR4-Targeting Radioligands Based on the Endogenous Antagonist EPI-X4 for Oncological Applications.Journal of medicinal chemistry · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Delivering peptides into cells could open up possibilities for targeting intracellular proteins. Although fatty acylation of peptide therapeutics improves their systemic half-life, it remains unclear how it influences their cellular uptake. Here, we demonstrate that a fatty acylated peptide exhibits enhanced cellular internalization and cytosolic distribution compared to the un-acylated version. By using a cystine-knot peptide as a model system, we report an efficient strategy for site-specific conjugation of fatty acids. Peptides modified with fatty acids of different chain lengths entered cells through clathrin-mediated and macropinocytosis pathways. The cellular uptake was mediated by the length of the hydrocarbon chain, with myristic acid conjugates displaying the highest distribution across the cytoplasm including the cytosol, and endomembranes of the ER, Golgi and mitochondria. Our studies demonstrate how fatty acylation improves the cellular uptake of peptides, and lay the groundwork for future development of bioactive peptides with enhanced intracellular distribution.
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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 Socratic graph.