Development of helix-based vasoactive intestinal peptide analogues: identification of residues required for receptor interaction.
Development of helix-based vasoactive intestinal peptide analogues: identification of residues required for receptor interaction.
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基于螺旋的血管活性肠肽类似物的开发：鉴定受体相互作用所需的残基。
DOI：
10.1021/bi00421a028
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发表时间：
1988
期刊：
影响因子：
2.9
通讯作者：
G. Velicelebi
中科院分区：
文献类型：
--
作者：
G. F. Musso;S. Patthi;Thomas C. Ryskamp;S. Provow;E. T. Kaiser;G. Velicelebi
基于残基6至残基28的区域在与膜受体结合时形成π-螺旋结构的假设，已经设计了几种VIP类似物。基于分布频率和结构同源性与几个序列相关的肽类似物的设计和建设的经验方法。设计、合成并分析了五种肽。一种类似物，模型5，含有天然疏水性和改变的亲水性表面，在与大鼠肺膜受体的结合中是有效的VIP激动剂（KD 1 = 11 +/-8pM，KD 2 = 6.4 +/-0.2nM; VIP KD 1 = 21 +/- 13 pM，KD 2 = 1.8 +/- 0.6 nM）和刺激豚鼠胰腺腺泡的淀粉酶释放（ED 50 = 90 pM; VIP ED 50 = 27 pM）。其他四种类似物的效力远低于VIP，但保留了全部的内在活性。我们的研究结果表明，该螺旋结构域的疏水表面（残基6-28）含有重要的氨基酸与受体的相互作用，而亲水表面上的氨基酸残基似乎并不强烈参与受体结合或信号转导。此外，在高亲和力结合的基础上，胰腺腺泡中淀粉酶释放的刺激似乎与更高亲和力的受体偶联。这些结果表明，基于推定的π-螺旋结构的构建的方法可以应用于VIP的生物活性类似物的设计。因此，我们已经确定了几个残基内的VIP序列是关键的受体结合使用这种方法。
Several VIP analogues have been designed on the basis of the hypothesis that the region from residue 6 to residue 28 forms a pi-helical structure when bound to membrane receptors. An empirical approach for the design and construction of analogues based upon distribution frequency and structural homology with several sequence-related peptides is presented. Five peptides were designed, synthesized, and analyzed. One analogue, model 5, containing the native hydrophobic and an altered hydrophilic surface, was an effective VIP agonist in both binding to rat lung membrane receptors (KD1 = 11 +/- 8 pM, KD2 = 6.4 +/- 0.2 nM; VIP KD1 = 21 +/- 13 pM, KD2 = 1.8 +/- 0.6 nM) and stimulation of amylase release from guinea pig pancreatic acini (ED50 = 90 pM; VIP ED50 = 27 pM). The four other analogues were considerably less potent than VIP, yet retained full intrinsic activity. Our results showed that the hydrophobic surface of this helical domain (residues 6-28) contains amino acids important for interaction with receptors, whereas amino acid residues on the hydrophilic surface do not seem to participate strongly in receptor binding or signal transduction. Furthermore, on the basis of high-affinity binding, the stimulation of amylase release in pancreatic acini appears to be coupled to the higher affinity receptors. These results suggest that an approach based on the construction of putative pi-helical structures can be applied to the design of biologically active analogues of VIP. Thus, we have identified several residues within the VIP sequence that are critical for receptor binding using this approach.
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分离的肝细胞和肝细胞膜囊泡上的胰高血糖素受体。
DOI：
--
发表时间：
1983
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bonnevie-Nielsen,V;Tager,HS
通讯作者：
Tager,HS
影响因子：
56.9
作者：
KAISER, ET;KEZDY, FJ
通讯作者：
KEZDY, FJ
β-内啡肽和相关肽激素和神经递质的结构特征。
影响因子：
21.1
作者：
Taylor,JW;Kaiser,ET
通讯作者：
Kaiser,ET
两亲肽激素及其类似物的表面特性：促肾上腺皮质激素释放因子和索瓦吉尼。
DOI：
10.1073/pnas.80.23.7070
发表时间：
1983
影响因子：
11.1
作者：
Lau,SH;Rivier,J;Vale,W;Kaiser,ET;Kézdy,FJ
通讯作者：
Kézdy,FJ
影响因子：
56.9
作者：
RIVIER, J;RIVIER, C;VALE, W
通讯作者：
VALE, W