Intra-Mitochondrial Self-Assembly to Overcome the Intracellular Enzymatic Degradation of L-peptides.

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 for both D and L isomeric forms. This outcome is contrary 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.