Design, Synthesis, and Anticancer Activity of Triptycene-Peptide Hybrids that Induce Paraptotic Cell Death in Cancer Cells.

We report on the design and synthesis of triptycene-peptide hybrids (TPHs), 5 , syn - 6 , and anti - 6 , which are conjugates of a triptycene core unit with two or three cationic KKKGG peptides (K: lysine and G: glycine) through a C 8 alkyl chain. It was discovered that syn - 6 and anti - 6 induce paraptosis, a type of programmed cell death (PCD), in Jurkat cells (leukemia T-lymphocytes). Mechanistic studies indicate that these TPHs induce the transfer of Ca 2+ from the endoplasmic reticulum (ER) to mitochondria, a loss of mitochondrial membrane potential (ΔΨ m ), tethering of the ER and mitochondria, and cytoplasmic vacuolization in the paraptosis processes.