期刊
BIOCONJUGATE CHEMISTRY
卷 33, 期 4, 页码 691-717出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.2c00076
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资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [17K08225, 18F18412, 20K05712]
- Uehara Memorial Foundation
- Tokyo Ohka Foundation for the Promotion of Science and Technology, Kanagawa, Japan
- Tokyo Biochemical Research Foundation, Tokyo, Japan
- Grants-in-Aid for Scientific Research [20K05712, 18F18412, 17K08225] Funding Source: KAKEN
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.
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.
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