Scientific Reference
Adipotide (Prohibitin-TP01)
Evidence profile: Preclinical, with limited uncontrolled human reports
Adipotide (prohibitin-TP01) is a synthetic peptidomimetic joining a nine-residue homing motif to a membrane-disrupting D-amino-acid sequence. The homing part, CKGGRAKDC, is a disulfide-closed cyclic peptide found by screening phage-display libraries for sequences that collect in the blood vessels of fat tissue. The other part, D-(KLAKLAK)2, is a synthetic amphipathic sequence built from D-amino acids and used in other conjugates as a pro-apoptotic module. Adipotide was studied in obese rodents and then in rhesus monkeys, where changes in kidney tubule function were reported. Human data are very limited, and most of the literature comes from the group that designed it.
Mechanism of Action
The CKGGRAKDC motif has been reported to bind prohibitin on the surface of endothelial cells lining blood vessels in white adipose tissue, and later work described annexin A2 as a partner in that binding. Once bound, the conjugate is taken up into the cell. The D-(KLAKLAK)2 domain is cationic and amphipathic; it has been reported to disrupt mitochondrial membranes and trigger apoptosis in the cells it enters, while its D-configuration makes it resistant to proteases. Animal studies examined the consequences for the blood supply of fat tissue. Prohibitin also has well-described roles inside cells, particularly in mitochondria, across many tissues.
Molecular Information
- Type: Chimeric peptide (L- and D-amino acids)
- Length: 25 amino acids
- Molecular weight: 2557.2 g/mol
- Molecular formula: C111H206N36O28S2