Fig. 1: CPPTACs promote the degradation of extracellular proteins through the endo-lysosomal pathway. | Nature Communications

Fig. 1: CPPTACs promote the degradation of extracellular proteins through the endo-lysosomal pathway.

From: Targeted degradation of cell surface proteins through endocytosis triggered by cell-penetrating peptide-small molecule conjugates

Fig. 1: CPPTACs promote the degradation of extracellular proteins through the endo-lysosomal pathway.

a Schematic of the CPPTACs platform designed for targeted degradation of cell-surface proteins. b CPP1-4 with different peptide sequences. c Fluorescence analysis of the cellular uptake and lysosomal degradation of NAP-650 (red) mediated by different Biotin-CPP in A549 cells in the presence or absence of lysosomal proteolytic activity inhibitor, chloroquine (CQ). d, e Fluorescence analysis of the inhibitory effect of Nystatin (50 μM), 7-KC (7-keto-cholesterol, 30 μM), CPZ (chlorpromazine, 10 μg/mL) or EIPA (ethylisopropylamiloride, 10 μg/mL) on the cellular uptake of NAP-650 (red) mediated by Biotin-CPP1 (d) or Biotin-CPP2 (e) in A549 cells. f, g Flow cytometry analysis (f) and fluorescence analysis (g) of the cellular uptake of NAP-650 (red) in A549 cells incubated with NAP-650 (0.5 μM) and Biotin-CPP1 at the indicated concentrations. Mean fluorescence intensity of NAP-650 relative to the untreated group was quantified (n = 3 biological replicates, means ± SD). h Fluorescence signals in A549 cells indicating the colocalization of NAP-FITC (green) with the early endosome marker (Rab5, red) mediated by Biotin-CPP1 or Biotin-CPP2. i Fluorescence signals in A549 cells indicating the colocalization of NAP-650 (red) with the lysosome marker (LysoTracker, green) mediated by Biotin-CPP1 or Biotin-CPP2. For c–e, g–i, the nuclei were labeled by DAPI (blue), scale bar, 10 μm. Source data are provided as a Source Data file.

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