A critical assessment of the synthesis and biological activity of p53/human double minute 2-stapled peptide inhibitors.

Cytosolic and nuclear accumulation was not an intrinsic property of the stapled peptide, but resulted from capture by the target Hdm2 after endo-lysosomal release. Considering the rather poor uptake of stapled peptides, further development should focus on increasing the efficiency of uptake of these peptides.