Scientific Reference
Adipotide
Evidence profile: Preclinical, with limited uncontrolled human reports
Adipotide, also catalogued as prohibitin-TP01, is a designed two-part molecule rather than something found in nature. One half is a homing sequence, CKGGRAKDC, a cyclic nine-residue peptide closed by a disulfide bond, which was picked out of phage-display libraries because it accumulates in the vasculature of white fat. The other half is D-(KLAKLAK)2, a synthetic amphipathic chain built from D-amino acids that has been used as a pro-apoptotic payload in other conjugates. Experiments were carried out in obese mice and then in rhesus monkeys, where changes in kidney tubule function were noted. Human data are very scarce, and most publications trace back to the group that engineered it.
Mechanism of Action
The homing motif is reported to engage prohibitin on the surface of endothelial cells in fat tissue vessels, with annexin A2 later described as a binding partner. After binding, the conjugate is internalised. Inside the cell the cationic, amphipathic D-(KLAKLAK)2 segment is reported to damage mitochondrial membranes and set off apoptosis, and because it is made of D-amino acids proteases do not readily degrade it. The animal work looked at what that did to the blood supply of fat. It is worth remembering that prohibitin is also an established intracellular protein, concentrated in mitochondria, found in a wide range of tissues.
Molecular Information
- Type: Chimeric peptide (L- and D-amino acids)
- Molecular weight: 2557.2 g/mol
- Molecular formula: C111H206N36O28S2