Cellular Uptake of A Taurine-Modified, Ester Bond-Decorated D-Peptide Derivative via Dynamin-Based Endocytosis and Macropinocytosis.

摘要: Most of the peptides used for promoting cellular uptake bear positive charges. In our previous study, we reported an example taurine (bearing negative charges in physiological conditions) D-peptides. Taurine, conjugated to a small D-peptide via ester bond, promotes this D-peptide. Particularly, intracellular carboxylesterase (CES) instructs self-assemble and form nanofibers, which largely disfavors efflux further enhances accumulation D-peptide, as supported by that addition CES inhibitors partially impaired molecule mammalian cell lines. Using dynamin 1, 2, 3 triple knockout (TKO) mouse fibroblasts, demonstrated cells took up macropinocytosis dynamin-dependent endocytosis. Imaging Drosophila larval blood derived from endocytic mutants confirmed involvement multiple endocytosis pathways. Electron microscopy (EM) indicated precursors can aggregates on surface facilitate macropinocytosis. EM also revealed significantly increased numbers vesicles cytosol. This work provides new insights into derivative delivery self-assembly