Therapeutic peptides: Targeting the mitochondrion to modulate apoptosis.
For many years, medical drug discovery has extensively exploited peptides as lead compounds. Currently, novel structures of therapeutic peptides are derived from active pre-existing peptides or from high-throughput screening, and optimized following a rational drug design approach. Molecules of interest may prove their ability to influence the disease outcome in animal models and must respond to a set of criteria based on toxicity studies, ease of administration, the cost of their synthesis, and logistic for clinical use to validate it as a good candidate in a therapeutic perspective. This applies to the potential use of peptides to target one central intracellular organelle, the mitochondrion, to modulate (i.e. activate or prevent) apoptosis. Putative mitochondrial protein targets and the strategies already elaborated to correct the defects linked to these proteins (overexpression, inactivation, mutation..., etc.) are described, and recent advances that led or may lead to the conception of therapeutic peptides via a specific action on these mitochondrial targets in the future are discussed.
Jacotot
Etienne
E
Theraptosis Research Laboratory, Theraptosis S A, Pasteur BioTop, 25-28 rue du Dr Roux, 75015, France.
Deniaud
Aurélien
A
Borgne-Sanchez
Annie
A
Touat
Zahia
Z
Briand
Jean-Paul
JP
Le Bras
Morgane
M
Brenner
Catherine
C
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects
D010455:Peptides