Conformational studies of antimetastatic laminin-1 derived peptides in different solvent systems, using solution NMR spectroscopy.
Conformational studies of antimetastatic laminin-1 derived peptides in different solvent systems, using solution NMR spectroscopy.
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使用溶液核磁共振波谱法对不同溶剂系统中的抗转移层粘连蛋白-1 衍生肽进行构象研究。
DOI：
10.1034/j.1399-3011.2003.21040.x
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Starkey,J
中科院分区：
文献类型：
--
作者：
Jaseja,M;Copié,V;Starkey,J
由于其在癌症进展中的关键作用，层粘连蛋白-1和67 kDa层粘连蛋白结合蛋白（67 kDa LBP）之间的相互作用一直是许多结构和生物学研究的焦点。 由于层粘连蛋白-1是如此大而复杂的分子，研究兴趣已经转向研究来自层粘连蛋白-1结合结构域的生物活性肽。两种感兴趣的肽，CDPGYIGSR（肽11）和YIGSR，均来源于层粘连蛋白-1的β 1链，已显示可阻断肿瘤细胞对基底膜的侵袭。将C-末端精氨酸取代为赖氨酸（保守取代）导致肽抗转移活性的丧失。基于游离肽构象的大量建模研究，这种生物活性的差异归因于YIGSR和YIGSK之间的结构差异。然而，“活性”游离肽骨架构象的性质一直是一个争论和争议的问题。为了测试结构建模声明的有效性，我们在三种不同的溶剂系统中通过二维溶液1H NMR光谱对两种层粘连蛋白-1衍生肽YIGSR和CDPGYIGSR沿着以及生物学上无活性的YIGSK类似物进行了详细的构象研究。在此，我们报告，虽然活性（YIGSR，CDPGYIGSR）和非活性（YIGSK）肽可以采取几个密切相关的构象在溶液中，这两种肽共享相似的构象偏好，并有没有显着的结构差异之间的活性和非活性肽，相反，以前报道的建模数据。我们得出结论，与已发表的模型相反，肽生物活性的基础不能归因于游离肽的明确定义的结构偏好。我们推断，YIGSR和YIGSK之间观察到的生物活性的差异主要源于精氨酸与赖氨酸侧链取代的化学性质，而不是由于游离肽构象的结构变化。
Due to its critical role in cancer progression, interactions between laminin‐1 and the 67 kDa Laminin‐Binding Protein (the 67 kDa LBP) have been the focus of a number of structural and biological studies. As laminin‐1 is such a large and complex molecule, research interests have turned to the investigation of bioactive peptides derived from binding domains of laminin‐1. Two peptides of interest, CDPGYIGSR (peptide 11) and YIGSR, both derived from the β1chain of laminin‐1, have been shown to block invasion of basement membranes by tumor cells. Substituting the C‐terminal arginine to lysine, a conservative substitution, results in a loss of peptide antimetastatic activity. This difference in bioactivity has been attributed, based on numerous modeling studies of free peptide conformations, to structural differences between YIGSR and YIGSK. Yet the nature of the ‘active’ free peptide backbone conformation has been a matter of debate and controversy. In order to test the validity of the structural modeling claims, we have undertaken detailed conformational studies of the two laminin‐1 derived peptides YIGSR and CDPGYIGSR along with the biologically inactive YIGSK analog by two‐dimensional solution1H NMR spectroscopy in three different solvent systems. Herein we report that although both the active (YIGSR, CDPGYIGSR) and the inactive (YIGSK) peptides can adopt several closely related conformations in solution, the two peptides share similar conformational preferences, and there are no significant structural differences between the active and inactive peptides, contrary to previously reported modeling data. We conclude that the basis of the peptide biological activity, in contrast to published models, cannot be attributed to well‐defined structural preferences of the free peptides. We infer that the difference in bioactivity observed between YIGSR and YIGSK originates primarily from the chemical nature of the arginine versus lysine sidechain substitution, rather than being due to a structural change in the free peptide conformations.
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通过 1H NMR 光谱定量蛋白质二级结构的简单技术
影响因子：
3.5
作者：
D. Wishart;D. Wishart;B. Sykes;F. Richards
通讯作者：
F. Richards
DOI：
10.1146/annurev.bb.20.060191.002511
发表时间：
1991
期刊：
Annual review of biophysics and biophysical chemistry
影响因子：
--
作者：
Dyson Hj;P. Wright
通讯作者：
Dyson Hj;P. Wright
层粘连蛋白在小鼠肿瘤细胞附着和转移中的作用。
影响因子：
11.2
作者：
V. Terranova;L. Liotta;R. G. Russo;G. Martin
通讯作者：
G. Martin
合成层粘连蛋白肽 CDPGYIGSR-NH2 抑制血管生成和肿瘤生长。
影响因子：
11.2
作者：
N. Sakamoto;M. Iwahana;Noriko G. Tanaka;Yasuaki Osada
通讯作者：
Yasuaki Osada
影响因子：
2.9
作者：
YOUNG, JK;HICKS, RP
通讯作者：
HICKS, RP