Development of an orexin-2 receptor selective agonist, [Ala(11), D-Leu(15)]orexin-B.

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作者：

S Asahi，SI Egashira，M Matsuda，H Iwaasa，A Kanatani，M Ohkubo，M Ihara，H Morishima

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摘要：

Investigation of -alanine and -amino acid replacement of orexin-B revealed that three -leucine residues at the positions of 11, 14, and 15 in orexin-B were important to show selectivity for the orexin-2 receptor (OX) over the orexin-1 receptor (OX). -Alanine substitution at position 11 and -leucine substitution at positions 14 and 15 maintained the potency of orexin-B to mobilize [Ca] in CHO cells expressing the OX, while their potency for the OX was significantly reduced. In combined substitutions, we identified that [Ala, -Leu]orexin-B showed a 400-fold selectivity for the OX (EC=0.13nM) over OX (EC=52nM). [Ala, -Leu]orexin-B is a beneficial tool for addressing the functional roles of the OX.AbstractHigh potent and selective orexin-2 receptor selective agonist peptides, [Ala]orexin-B and [Ala, -Leu]orexin-B, were found from systematic -alanine and -amino acid replacement of orexin-B.

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关键词：

Animals Humans Rats CHO Cells Intracellular Signaling Peptides and Proteins Neuropeptides Receptors, G-Protein-Coupled Receptors, Neuropeptide Amino Acid Substitution Protein Structure, Secondary