Brauns Olaf, Brauns Simone, Zimmermann Bodo, Jahn Olaf, Spiess Joachim
Department of Molecular Neuroendocrinology, Max Planck Institute for Experimental Medicine, Hermann Rein Street 3, Goettingen, Germany.
Peptides. 2002 May;23(5):881-8. doi: 10.1016/s0196-9781(02)00014-1.
The role of the N-terminal domains of corticotropin-releasing factor (CRF) and CRF-like peptides in receptor subtype selectivity, ligand affinity and biological potency was investigated. Therefore, human CRF(12-41), human URP(12-38) and antisauvagine-30 (aSvg) were N-terminally prolonged by consecutive addition of one or two amino acids. The peptides obtained were tested for their binding affinities to rat CRF1 and murine CRF(2beta) receptor, and their capability to stimulate cAMP-release by HEK cells producing either receptor. It was observed that human CRF N-terminally truncated by eight residues was bound with high affinity to CRF2 receptor (Ki=5.4nM), whereas affinity for CRF1 receptor was decreased (Ki=250 nM). A similar shift of affinity was found with sauvagine (Svg) analogs. Truncation of human URP analogs did not affect their preference for CRF(2beta) receptor, but reduced their affinity. Changes in affinity were positively correlated with changes in potency. These results indicated that CRF1 receptor was more stringent in its structural requirements for ligands to exhibit high affinity binding than CRF(2beta) receptor.
研究了促肾上腺皮质激素释放因子（CRF）和CRF样肽的N端结构域在受体亚型选择性、配体亲和力和生物学活性方面的作用。因此，通过连续添加一个或两个氨基酸对人CRF（12-41）、人URP（12-38）和抗 sauvagine-30（aSvg）进行N端延长。对所得肽进行了与大鼠CRF1和小鼠CRF（2β）受体的结合亲和力测试，以及它们刺激产生任一受体的HEK细胞释放cAMP的能力测试。观察到N端截短8个残基的人CRF与CRF2受体具有高亲和力结合（Ki = 5.4 nM），而对CRF1受体的亲和力降低（Ki = 250 nM）。在sauvagine（Svg）类似物中也发现了类似的亲和力变化。人URP类似物的截短不影响它们对CRF（2β）受体的偏好，但降低了它们的亲和力。亲和力的变化与活性的变化呈正相关。这些结果表明，CRF1受体对配体表现出高亲和力结合的结构要求比CRF（2β）受体更严格。
