Intra-mitochondrial self-assembly to overcome the intracellular enzymatic degradation of l-peptides

Abstract

The design of peptide-based therapeutics is generally based on the replacement of L-amino acids with D-isomers to obtain improved therapeutic efficiency. However, D-isomers are expensive and frequently induce undesirable immune responses. In the present work, we demonstrate that an intra-mitochondrially self-assembling amphiphilic peptide exhibits analogous activity in both D- and L-isomeric forms. This outcome is in contrast to the general observation considering higher therapeutic efficiencies of D-isomers compared with L-analogues. This suggests that L-peptides overcome proteolytic degradation during intra-mitochondrial self-assembly both in vitro and in vivo.