Abstract
Extensive internalization into endothelial cells has been found for a water soluble amphipathic 26-mer beta-sheet peptide (FLUOS-DPKGDPKGVTVTVTVTVTGKGDPKPD-NH2; VT5). With the D-Val13,D-Thr14 di-D-amino acid analog of VT5 (DD-VT5), exhibiting an identical primary structure but no propensity to adopt a beta-sheet conformation, only about 5% of the cellular uptake of VT5 was found. The mechanism of entry of VT5 into the cells remained unclear, but proved to be energy, temperature and pH dependent and, therefore, clearly distinct from that reported for helical amphipathic peptides. No detectable cytotoxicity, high solubility in water and the found extensive entry into endothelial cells make VT5 appear a good lead for developing new types of vectors for delivering oligonucleotides and peptides into intact cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Aorta
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Biological Transport
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Brefeldin A
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Cattle
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Cell Survival / drug effects
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Cells, Cultured
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Cyclopentanes / pharmacokinetics
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Deoxyglucose / pharmacology
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Endothelium, Vascular / metabolism*
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Fluoresceins / metabolism
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Fluorescent Dyes / pharmacokinetics
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Hydrogen-Ion Concentration
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Isoquinolines / pharmacokinetics
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Molecular Sequence Data
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Monensin / pharmacology
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Peptides / chemical synthesis
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Peptides / chemistry*
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Peptides / pharmacokinetics*
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Peptides / pharmacology
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Protein Structure, Secondary*
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Proteins / chemical synthesis
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Proteins / chemistry*
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Proteins / genetics
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Proteins / pharmacokinetics*
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Solubility
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Temperature
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Vincristine / pharmacology
Substances
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Cyclopentanes
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Fluoresceins
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Fluorescent Dyes
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Isoquinolines
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Peptides
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Proteins
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VT5 peptide
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Brefeldin A
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Vincristine
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Monensin
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lucifer yellow
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Deoxyglucose