Neuropeptide Y and neuropeptide Y18-36. Structural and biological characterization.
Neuropeptide Y and neuropeptide Y18-36. Structural and biological characterization.
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神经肽Y和神经肽Y18-36。
DOI：
10.1111/j.1399-3011.1989.tb00677.x
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Rivier,J
中科院分区：
文献类型：
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作者：
Boublik,J;Scott,N;Taulane,J;Goodman,M;Brown,M;Rivier,J
神经肽Y（NPY）是一种36个残基的肽酰胺，已被许多研究表明是一种有效的血管收缩剂。为了了解这种作用的结构要求，我们以前合成了许多NPY片段。已经表明，从N末端连续缺失导致具有降低的高血压活性的肽。在本研究中，我们提供的数据支持了两个片段（NPY 17 - 36和NPT 18 - 36）在体内具有显著的抗肿瘤作用的意外发现。该作用具有剂量依赖性（数据未显示），并且在NPY 19 - 36中也观察到了较低程度的抗肿瘤作用，但在NPY 16 - 36或NPY 20 - 36中没有观察到。然而，它比NPY的高血压作用起效慢，持续时间长。这些不同的作用动力学可能表明NPY和NPY 18 - 36通过不同的机制起作用。使用圆二色性进行结构研究。虽然发现NPY在水性缓冲液和三氟乙醇（TFE）中呈现有序的螺旋结构，但需要水性缓冲液中的30% TFE才能诱导NPY 18 - 36的大量螺旋。这种结构研究表明，NPY和NPY 18 - 36在到达富含脂质的受体环境后呈现有序构象。
Neuropeptide Y (NPY), a 36‐residue peptide amide, has been shown by numerous studies to be a potent vasoconstrictor. In order to gain an appreciation of the structural requirements for this action, we have previously synthesized a number of fragments of NPY. It had been shown that sequential deletions from theN‐terminus resulted in peptides with decreasing hypertensive activity. In the present study we present data supporting the unexpected finding of two fragments, NPY17‐36and NPT18‐36with substantialhypotensiveactionin vivo.This action was dose dependent (data not shown) and was also observed to a lesser extent with NPY19‐36but not NPY16‐36or NPY20‐36. It was, however, slower in onset and of longer duration than the hypertensive action of NPY. These differing kinetics of action may suggest that NPY and NPY18‐36act through different mechanisms. Structural studies using circular dichroism were performed. While NPY was found to assume an ordered helical structure in both aqueous buffer and trifluoroethanol (TFE), 30% TFE in aqueous buffer was required to induce substantial helicity for NPY18‐36. This structural investigation suggests that both NPY and NPY18‐36assume an ordered conformation upon reaching the lipid rich receptor environment.