大鼠甲状旁腺激素2受体拮抗剂的研发
Development of a rat parathyroid hormone 2 receptor antagonist.
作者信息
Kuo Jonathan, Usdin Ted B
机构信息
National Institute of Mental Health, Laboratory of Genetics, Building 35, Room 1B-415, Convent Drive, MSC 3728, Bethesda, MD 20892, USA.
出版信息
Peptides. 2007 Apr;28(4):887-92. doi: 10.1016/j.peptides.2006.12.002. Epub 2007 Jan 4.
Abstract
The parathyroid hormone 2 (PTH2) receptor is a Family B G-protein coupled receptor most highly expressed within the brain. Current evidence suggests that tuberoinfundibular peptide of 39 residues (TIP39) is the PTH2 receptor's endogenous ligand. To facilitate investigation of the physiological function of the PTH2 receptor/TIP39 system, we have developed a novel PTH2 receptor antagonist, by changing several residues within the amino terminal domain of TIP39. Histidine(4), tyrosine(5), tryptophan(6), histidine(7)-TIP39 binds the PTH2 receptor with high affinity, has over 30-fold selectivity for the rat PTH2 receptor over the rat PTH1 receptor and displays no detectable agonist activity. This ligand should be useful for in vivo investigation of PTH2 receptor function.
摘要
甲状旁腺激素2（PTH2）受体是B族G蛋白偶联受体，在大脑中表达最为丰富。目前的证据表明，39个氨基酸残基的结节漏斗肽（TIP39）是PTH2受体的内源性配体。为了便于研究PTH2受体/TIP39系统的生理功能，我们通过改变TIP39氨基末端结构域内的几个残基，开发了一种新型的PTH2受体拮抗剂。组氨酸（4）、酪氨酸（5）、色氨酸（6）、组氨酸（7）-TIP39以高亲和力结合PTH2受体，对大鼠PTH2受体的选择性比对大鼠PTH1受体高30倍以上，且未表现出可检测到的激动剂活性。这种配体应有助于对PTH2受体功能进行体内研究。
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