The CART (cocaine- and amphetamine-regulated transcript) peptide is an anorexigenic neuropeptide that acts in the hypothalamus. The receptor and the mechanism of action of this peptide are still unknown. In our previous study, we showed that the CART peptide binds specifically to PC12 rat pheochromocytoma cells in both the native and differentiated into neuronal phenotype. Two biologically active forms, CART(55-102) and CART(61-102), with equal biological activity, contain three disulfide bridges. To clarify the importance of each of these disulfide bridges in maintaining the biological activity of CART(61-102), an Ala scan at particular S-S bridges forming cysteines was performed, and analogs with only one or two disulfide bridges were synthesized. In this study, a stabilized CART(61-102) analog with norleucine instead of methionine at position 67 was also prepared and was found to bind to PC12 cells with an anorexigenic potency similar to that of CART(61-102). The binding study revealed that out of all analogs tested, [Ala(68,86)]CART(61-102), which contains two disulfide bridges (positions 74-94 and 88-101), preserved a high affinity to both native PC12 cells and those that had been differentiated into neurons. In food intake and behavioral tests with mice after intracerebroventricular administration, this analog showed strong and long-lasting anorexigenic potency. Therefore, the disulfide bridge between cysteines 68 and 86 in CART(61-102) can be omitted without a loss of biological activity, but the preservation of two other disulfide bridges and the full-length peptide are essential for biological activity.

• MeSH
• anorektika chemie   farmakologie   MeSH
• buňky PC12 MeSH
• cystin chemie   MeSH
• kompetitivní vazba MeSH
• krysa rodu Rattus MeSH
• lokomoce účinky léků   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nocicepce účinky léků   MeSH
• peptidové fragmenty chemie   farmakologie   MeSH
• přijímání potravy účinky léků   MeSH
• proteiny nervové tkáně chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anorektika MeSH
• cocaine- and amphetamine-regulated transcript peptide (62-102), human MeSH Prohlížeč
• cystin MeSH
• peptidové fragmenty MeSH
• proteiny nervové tkáně MeSH