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 Ca2+ from the endoplasmic reticulum (ER) to mitochondria, a loss of mitochondrial membrane potential (Delta Psi(m)), tethering of the ER and mitochondria, and cytoplasmic vacuolization in the paraptosis processes.

Automated summary

In this study, triptycene-peptide hybrids were designed and synthesized, and it was found that certain compounds with conjugated structures induced a new type of cell death called paraptosis in leukemia T-lymphocytes. Mechanistic studies revealed that these compounds induced a series of cellular processes leading to paraptosis.