ArticleBiochemistry2010
Modeling of the endosomolytic activity of HA2-TAT peptides with red blood cells and ghosts.
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Comparison of Cell-Penetrating and Fusogenic TAT-HA2 Peptide Performance in Peptideplex, Multicomponent, and Conjugate siRNA Delivery Systems.ACS omega · 2024Article
- Review
- Hydrophobicity is a key determinant in the activity of arginine-rich cell penetrating peptides.Scientific reports · 2022Article
- Rapidly Transducing and Spatially Localized Magnetofection Using Peptide-Mediated Non-Viral Gene Delivery Based on Iron Oxide Nanoparticles.ACS applied nano materials · 2021Article
- Novel pH Selective, Highly Lytic Peptides Based on a Chimeric Influenza Hemagglutinin Peptide/Cell Penetrating Peptide Motif.Molecules (Basel, Switzerland) · 2019Article
- Trapped! A Critical Evaluation of Methods for Measuring Total Cellular Uptake versus Cytosolic Localization.Bioconjugate chemistry · 2019Review
- Endosomal Escape and Cytosolic Penetration of Macromolecules Mediated by Synthetic Delivery Agents.Bioconjugate chemistry · 2019Review
- Efficient Delivery of Macromolecules into Human Cells by Improving the Endosomal Escape Activity of Cell-Penetrating Peptides: Lessons Learned from dfTAT and its Analogs.Biomolecules · 2018Review
- Evaluation of the bioactivity of a mastoparan peptide from wasp venom and of its analogues designed through targeted engineering.International journal of biological sciences · 2018Article
- A Novel p19 Fusion Protein as a Delivery Agent for Short-interfering RNAs.Molecular therapy. Nucleic acids · 2016Article
- Modular analysis of hipposin, a histone-derived antimicrobial peptide consisting of membrane translocating and membrane permeabilizing fragments.Biochimica et biophysica acta · 2014Article
- Study on characteristics of in vitro culture and intracellular transduction of exogenous proteins in fibroblast cell line of Liaoning cashmere goat.Molecular biology reports · 2013Article
- Unusual titration of the membrane-bound artificial hemagglutinin fusion peptide.European biophysics journal : EBJ · 2012Article
- Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges.Pharmaceuticals (Basel, Switzerland) · 2012Review
- Protein transduction in human cells is enhanced by cell-penetrating peptides fused with an endosomolytic HA2 sequence.Peptides · 2012Article
- A HA2-Fusion tag limits the endosomal release of its protein cargo despite causing endosomal lysis.Biochimica et biophysica acta · 2011Article
- Synergy between cell-penetrating peptides and singlet oxygen generators leads to efficient photolysis of membranes.Photochemistry and photobiologyArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
HA2-TAT is a peptide-based delivery agent that combines the pH-sensitive HA2 fusion peptide from influenza and the cell-penetrating peptide TAT from HIV. This chimeric peptide is engineered to induce the cellular uptake of macromolecules into endosomes via the TAT moiety and to respond to the acidifying lumen of endosomes to cause membrane leakage and release of macromolecules into cells via the HA2 moiety. The question of how HA2 and TAT affect the properties of one another remains, however, unanswered, and the behavior of the peptide inside endosomes is mostly uncharacterized. To address these issues, the binding and membrane leakage activity of a glutamic acid-enriched analogue E5-TAT was assessed with red blood cells and giant unilamellar vesicles as membrane models for endosomes. Hemolysis and microscopy assays reveal that E5-TAT binds to membranes in a pH-dependent manner and causes membrane leakage by inducing the formation of pores through which macromolecules can escape. The TAT moiety contributes to this activity by causing a shift in the pH response of E5 and by binding to negatively charged phospholipids. On the other hand, TAT binding to glycosaminoglycans reduces the lytic activity of E5-TAT. Addition of TAT to the C-terminus of E5 can therefore either increase or inhibit the activity of E5 depending on the cellular components present at the membrane. Taken together, these results suggest a model for the endosomolytic activity of the peptide and provide the basis for the molecular design of future delivery agents.
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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.