Simple Branched Arginine-Based Structures can Enhance the Cellular Uptake of Peptide Cargos |
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Authors: | Brendon Y Chua Weiguang Zeng David C Jackson |
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Institution: | (1) Department of Microbiology & Immunology, The University of Melbourne, Parkville, Victoria, 3010, Australia |
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Abstract: | In an attempt to design delivery vehicles to enable epitope-based vaccine uptake, we investigated the properties of a variety
of synthetic, branched cationic structures. We found that branched compounds based on arginine or lysine were able to facilitate
internalization of peptide cargo into cells to different degrees. Branched constructs containing only two arginine residues
(R2) were not only able to bind to cells more efficiently than constructs with two lysine residues (K2) but were also internalized within vesicle like compartments in the cell. The extent of binding and uptake was enhanced when
additional arginine residues were incorporated to form a tetra arginine construct (R4). An investigation into the kinetics and dose dependence of cellular uptake of these arginine-based constructs demonstrated
that binding and internalization is a rapid and efficient event. We also found uptake of the peptide epitope TYQRTRALV was
enhanced when it was coupled to R4. This approach may prove useful for introducing peptide epitopes into antigen presenting cells as self-adjuvanting structures
and also for delivery of other peptides into different specialized cells. |
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Keywords: | synthetic vaccines cell entry peptide cargo |
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