ArticleThe Journal of biological chemistry2017
An l- to d-Amino Acid Conversion in an Endosomolytic Analog of the Cell-penetrating Peptide TAT Influences Proteolytic Stability, Endocytic Uptake, and Endosomal Escape.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 91 citations in OpenAlex.
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- Review
- Receptor-Mediated Shuttling of a D-Amino Acid Peptide Achieves High Nanomolar Cytosolic Concentrations.Journal of the American Chemical Society · 2026Article
- Functional Peptide-Based Biomaterials for Pharmaceutical Application: Sequences, Mechanisms, and Optimization Strategies.Journal of functional biomaterials · 2026Review
- Topical Ocular Drug Delivery: The Impact of Permeation Enhancers.Pharmaceutics · 2025Review
- Mechanistic Insights into the Tools for Intracellular Protein Delivery.Chem & bio engineering · 2025Review
- In Vitro Profiling of the Antiviral Peptide TAT-I24.International journal of molecular sciences · 2024Article
- Plasma membrane damage limits cytoplasmic delivery by conventional cell penetrating peptides.PloS one · 2024Article
- Cell-Surface-Retained Peptide Additives for the Cytosolic Delivery of Functional Proteins.Journal of the American Chemical Society · 2023Article
- Elucidating the Impact of Payload Conjugation on the Cell-Penetrating Efficiency of the Endosomal Escape Peptide dfTAT: Implications for Future Designs for CPP-Based Delivery Systems.Bioconjugate chemistry · 2023Article
- Topoisomeric Membrane-Active Peptides: A Review of the Last Two Decades.Pharmaceutics · 2023Review
- Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules.Pharmaceutics · 2023Review
- In-Cell Penetration Selection-Mass Spectrometry Produces Noncanonical Peptides for Antisense Delivery.ACS chemical biology · 2023Article
- Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System.Pharmaceutics · 2022Review
- Cell-Penetrating d-Peptides Retain Antisense Morpholino Oligomer Delivery Activity.ACS bio & med chem Au · 2022Article
- Design of Membrane Active Peptides Considering Multi-Objective Optimization for Biomedical Application.Membranes · 2022Review
- Protease-Resistant Peptides for Targeting and Intracellular Delivery of Therapeutics.Pharmaceutics · 2021Review
- siRNA delivery using intelligent chitosan-capped mesoporous silica nanoparticles for overcoming multidrug resistance in malignant carcinoma cells.Scientific reports · 2021Article
- Development of D-melittin polymeric nanoparticles for anti-cancer treatment.Biomaterials · 2021Article
- Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects.Journal of medicinal chemistry · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cell-penetrating peptides (CPPs) are well established as delivery agents for otherwise cell-impermeable cargos. CPPs can also theoretically be used to modulate intracellular processes. However, their susceptibility to proteolytic degradation often limits their utility in these applications. Previous studies have explored the consequences for cellular uptake of converting the residues in CPPs from l- to d-stereochemistry, but conflicting results have been reported and specific steps en route to intracellular activity have not been explored. Here we use dimeric fluorescence TAT as a model CPP to explore the broader consequences of l- to d-stereochemical conversion. We show that inversion of chirality provides protease resistance without altering the overall mode of cellular entry, a process involving endocytic uptake followed by endosomal escape and cytosolic access. However, whereas inversion of chirality reduces endocytic uptake, the d-peptide, once in the endosome, is significantly more prone to escape than its l-counterpart. Moreover, the d-peptide is retained in the cytosol of cells for several days, whereas the l-peptide is degraded within hours. Notably, while the l-peptide is relatively innocuous to cells, the d-peptide exerts a prolonged anti-proliferative activity. Together, our results establish connections between chirality, protease resistance, cellular penetration, and intracellular activity that may be useful for the development of future delivery agents with improved properties.
Indexed as
Identifiers
What OpenQuestion holds
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.