Structural Targeting of Fat Vasculature and Apoptotic Kinetics with Adipotide (FTPP)

Journal Context: The Journal of Clinical Investigation | Identifiers: DOI: 10.1172/JCI200421515 / PMID: 15233934

Principal Investigators: Kolonin, M. G., Pasqualini, R., & Arap, W. (Surface Display and Structural Biology Program, University of Texas)

Methodology: In vitro and in vivo tracking using fluorescently tagged Adipotide variants introduced to rodent lines fed a high-fat diet. Tissues were histologically staged using TUNEL staining to detect real-time DNA fragmentation and evaluate cell death rates inside the endothelial walls of fat-tissue capillaries.

Key Findings: The study verified that the CKGGRAKDC homing sequence binds with high specificity to prohibitin, a membrane protein heavily expressed on the surface of blood vessels feeding white fat tissue. Once locked onto the cell, the peptide is pulled inside, allowing its secondary payload—the D(KLAKLAK)₂ sequence—to physically rupture the cell's mitochondria. This action triggered immediate endothelial apoptosis, causing the blood vessels to collapse and forcing the surrounding fat tissue to undergo rapid structural atrophy.