- Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells
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The in vivo utility of technologies employing cell penetrating peptides and bioportides may be compromised by the general capacity of polycationic peptides to activate mast cell secretion. Moreover, the same technologies could be exploited in a clinical setting either to directly modulate intrinsic exocytotic mechanisms or to load mast cells with bioactive cargoes. Comparative investigations identified two cell penetrating vectors, Tat and C105Y, which readily translocate into mast cells without inducing receptor-independent exocytosis. Efficient Tat transduction also enabled the intracellular delivery and accumulation of cargoes within discrete intracellular compartments. A tetramethylrhodamine-Tat conjugate is effectively translocated into the secretory lysosomes of RBL-2H3 cells. In contract, the intracellular delivery of avidin, as a non-covalent complex with a biotinylated Tat vector, is also efficient but the protein is predominantly accumulated outside of secretory lysosomes. Significantly, both cargoes can be subsequently released following mast cell stimulation either by mastoparan, a wasp venom secretagogue, or by the physiological mechanism of antigen-induced aggregation of high affinity IgE receptors. These studies indicate that mast cells could be exploited to direct the delivery of bioactive agents to disease sites as an innovative cell-mediated therapy.
- Howl, John,Jones, Sarah
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p. 108 - 117
(2015/02/19)
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- Synthesis of a Wasp Venom Tetradecapeptide, Mastoparan, with a New Cleaving System for 4-Methoxy-2,2,6-trimethylbenzenesulfonyl (Mtr) Amino-Protecting Group
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The 4-methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr) group was introduced for protection of the ε-amino function of lysine and its acid lability was examined.The cleavage of Lys(Mtr) was accelerated by addition of methyl sulfide, as a second scavenger, to methanesulfonic acid-containing trifluoroacetic acid-thioanisole.In order to examine the usefulness of the new cleaving system with methyl sulfide, a wasp venom peptide, mastoparan, was synthesized.This system was found to give a highly pure product in good yield.Keywords - 4-methoxy-2,3,6-trimethylbenzenesulfonyl (Mtr); Nε-4-methoxy-2,3,6-trimethylbenzenesulfonyllysine; methanesulfonic acid-trifluoracetic acid-thioanisole-methyl sulfide deprotection; mastoparan; wasp venom peptide
- Saito, Kazuki,Higashijima, Tsutomu,Miyazawa, Tatsuo,Wakimasu, Mitsuhiro,Fujino, Masahiko
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p. 2187 - 2193
(2007/10/02)
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