A Novel Cyclic Mobile Transporter Can Induce Apoptosis by Facilitating Chloride Anion Transport into Cells

ACS Omega
Goutam KulsiKrishnananda Chattopadhyay

Abstract

We report here the preparation of an aminoxy amide-based pseudopeptide-derived building block using furanoid sugar molecules. Through the cyclo-oligomerization reaction, we generate a hybrid triazole/aminoxy amide macrocycle using the as-prepared building block. The novel conformation of the macrocycle has been characterized using NMR and molecular modeling studies, which show a strong resemblance of our synthesized compound to d-,l-α-aminoxy acid-based cyclic peptides that contain uniform backbone chirality. We observe that the macrocycle can efficiently and selectively bind Cl- ion and transport Cl- ion across a lipid bilayer. 1H NMR anion binding studies suggest a coherent relationship between the acidity of aminoxy amide N-H and triazole C-H proton binding strength. Using time-based fluorescence assay, we show that the macrocycle acts as a mobile transporter and follows an antiport mechanism. Our synthesized macrocycle imposes cancer cell death by disrupting ionic homeostasis through Cl- ion transport. The macrocycle induced cytochrome c leakage and changes in mitochondrial membrane potential along with activation of family of caspases, suggesting that the cellular apoptosis occurs through a caspase-dependent intrinsic path...Continue Reading

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Citations

May 28, 2021·Chembiochem : a European Journal of Chemical Biology·Arundhati Roy, Pinaki Talukdar

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Methods Mentioned

BETA
NMR
FACS
flow cytometry
dynamic light scattering
size exclusion chromatography
Assay
Fluorescence
ELISA

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