Coassembly of Enantiomeric Peptides Inside Mitochondria for Cancer Therapy

Abstract

Homochiral assembly of amphiphilic peptides consisting either D- or L-enantiomers inside the living cells are emerging as an attractive strategy for different biological implications including therapeutics. However, less attention is given for the heterochiral assembly of peptides consisting both D- and L-isomers. Heterochiral assembly containing both D- and L-isomers (racemates) could create wonders in their biological impact since the assembly of racemates often results in altered properties compared with enantiomers such as faster kinetics, higher mechanical strength and enzymatic stability. In here, we have monitored altered morphological and biological properties of a short peptide amphiphile, Mito-FF upon their co-assembly with mirror pair, Mito-ff. Mito-FF is an intra mitochondrial self-assembling peptide amphiphile, which induce cancer cell apoptosis followed by mitochondrial damage upon intra mitochondrial fibrillation. Mito-FF upon co-assembly with Mito-ff induced thick fibrous bundle of diameter upto 100 nm, while enantiomers form fiber of diameter ~ 10 nm. The co administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption than enantiomers both in vitroand in vivoas a result of intra mitochondrial racemic co-assembly to form thicker Mito-rac fibrous bundles.