Development of structure-activity relationship of orexins: possible roles of three regions of orexin-B
2004
Orexin-A and orexin-B are newly identified neuropeptides which are involved in a wide variety of physiological functions. The actions of orexins are mediated by the activation of the orexin-1 and orexin-2 receptors, whichhave distinct physiological roles. Orexin-B shows a relative selectivity for the orexin-2 receptor. Efforts to address the structure-activity relationship of orexin-B have shown that it is divided into three functional regions based on the potency of the several modified peptides as well as the sequence homology between several species. The C-terminal region is essentially required for receptor activation. The middle region is thought to play a role in receptor selectivity. The N-terminal region may be involved in the difference between the physiological functions of orexin-A and orexin-B. Furthermore, serveral lines of evidence support the ides that three leucine residues on the middle region could be important for the potency and selectivity of orexins, both functionally and structurally.
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