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

The design of peptide-based therapeutics is generally based on the replacement ofl-amino acids withd-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 bothd- andl-isomeric forms. This outcome is in contrast to the general observation considering higher therapeutic efficiencies ofd-isomers compared withl-analogues. This suggests thatl-peptides overcome proteolytic degradation during intra-mitochondrial self-assembly bothin vitroandin vivo.