Agonists and Partial Antagonists Acting on the Leptin—Leptin Receptor Interface
Leptin is a neurohormone regulating energy balance and food intake acting in the hypothalamus . Leptin can also modulate immune response, fertility, and hematopoiesis, acting as a mitogen, metabolic regulator, or pro-angiogenic factor. Both leptin and the leptin receptor (ObR) are overexpressed in breast and colorectal cancer . An ever increasing wealth of evidence suggests that leptin is a novel pharmaceutical target for diseases related to leptin overabundance (cancer) as well as deficit (lipodystrophy or anorexia-related infertility). The full form of ObR is 1,165 amino acids long and contains the extracellular, transmembrane, and intracellular domains. The extracellular domain binds ligand, whereas the intracellular tail recruits and activates signaling substrates. Leptin appears to interact with its receptor at three discontinuous surfaces, at each with two arms . Interfering with these surfaces may decrease or increase the efficiency of downstream ObR...
KeywordsMammary Epithelial Cell Line Normal Mammary Epithelial Cell Alanine Mutant Regulate Energy Balance Partial Antagonist
This work was supported by the Formula Fund of the PA Department of Health and by the Sbarro Health Research Organization.