Simple Branched ArginineBased Structures can Enha

Authors: Brendon Y Chua Weiguang Zeng David C Jackson

Publish Date: 2007/01/26

Volume: 13, Issue: 3, Pages: 431-437

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Abstract

In an attempt to design delivery vehicles to enable epitopebased 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 argininebased 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 selfadjuvanting structures and also for delivery of other peptides into different specialized cells

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