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基于结构与功能关系的蛋白质设计及其临床应用

[Protein design based on the structure and function relationship and its clinical application].

作者信息

Titani K

机构信息

Division of Biomedical Polymer Science, Fujita Health University.

出版信息

Rinsho Ketsueki. 1994 Apr;35(4):323-31.

PMID:8028175
Abstract

Proteins are biopolymers which are directly involved in biological functions. Since their defects cause various diseases, proteins have been studied for a long time as the subjects of both basic and clinical medicine. Recent development of the genetic recombinant technique has made it possible to replace, add or delete any amino acid residue or any peptide portion in a protein. By utilizing this technique, we are now able to clarify more precisely than ever the structure and function relationship of a protein, and also to create various novel artificial proteins for the clinical use. In this article, I describe the proteins which are involved in blood coagulation and fibrinolysis and the regulation, and the current clinical application of the recombinant proteins. I also describe our new protein engineering technique for creation of artificial cell adhesive proteins by grafting the Arg-Gly-Asp Ser (RGDS) cell recognition signal, which was identified first in fibronectin and later in various plasma and extracellular matrix proteins. The physiological functions and possible clinical application of these artificial cell adhesive proteins thus created are also discussed.

摘要

蛋白质是直接参与生物功能的生物聚合物。由于其缺陷会引发各种疾病,蛋白质长期以来一直是基础医学和临床医学的研究对象。基因重组技术的最新发展使得在蛋白质中替换、添加或删除任何氨基酸残基或任何肽段成为可能。通过利用这项技术,我们现在能够比以往更精确地阐明蛋白质的结构与功能关系,还能够制造出各种用于临床的新型人工蛋白质。在本文中,我描述了参与血液凝固、纤维蛋白溶解及其调节的蛋白质,以及重组蛋白质的当前临床应用。我还描述了我们通过嫁接Arg-Gly-Asp Ser(RGDS)细胞识别信号来创建人工细胞粘附蛋白的新蛋白质工程技术,该信号最初在纤连蛋白中被发现,后来在各种血浆和细胞外基质蛋白中也被发现。本文还讨论了由此产生的这些人工细胞粘附蛋白的生理功能和可能的临床应用。

相似文献

1
[Protein design based on the structure and function relationship and its clinical application].基于结构与功能关系的蛋白质设计及其临床应用
Rinsho Ketsueki. 1994 Apr;35(4):323-31.
2
Artificial cell adhesive proteins engineered by grafting the Arg-Gly-Asp cell recognition signal: factors modulating the cell adhesive activity of the grafted signal.通过嫁接精氨酸-甘氨酸-天冬氨酸细胞识别信号构建的人工细胞黏附蛋白:调控嫁接信号细胞黏附活性的因素
J Biochem. 1991 Sep;110(3):381-7. doi: 10.1093/oxfordjournals.jbchem.a123590.
3
Peptide array-based interaction assay of solid-bound peptides and anchorage-dependant cells and its effectiveness in cell-adhesive peptide design.基于肽阵列的固相结合肽与贴壁依赖性细胞的相互作用测定及其在细胞黏附肽设计中的有效性。
J Biosci Bioeng. 2006 Jun;101(6):485-95. doi: 10.1263/jbb.101.485.
4
[Structure and function of a cell adhesive signal, Arg-Gly-Asp sequence].[一种细胞黏附信号——精氨酸-甘氨酸-天冬氨酸序列的结构与功能]
Tanpakushitsu Kakusan Koso. 1997 Jan;42(1):31-41.
5
[Fibronectin--synergy cell recognition site].[纤连蛋白——协同细胞识别位点]
Rinsho Byori. 1996 Dec;44(12):1119-24.
6
Cell-binding domain context affects cell behavior on engineered proteins.细胞结合域背景影响工程蛋白上的细胞行为。
Biomacromolecules. 2005 Jan-Feb;6(1):318-23. doi: 10.1021/bm049627q.
7
Superfibronectin is a functionally distinct form of fibronectin.超纤连蛋白是纤连蛋白在功能上的一种独特形式。
Nature. 1994 Jan 13;367(6459):193-6. doi: 10.1038/367193a0.
8
Conformational changes in adhesive proteins modulate their adhesive function.粘附蛋白的构象变化会调节其粘附功能。
Thromb Haemost. 1995 Jul;74(1):253-7.
9
Chemokines regulate T cell adherence to recombinant adhesion molecules and extracellular matrix proteins.趋化因子调节T细胞对重组黏附分子和细胞外基质蛋白的黏附。
J Immunol. 1996 Feb 1;156(3):932-8.
10
Matrix cell adhesion activation by non-adhesion proteins.非粘附蛋白介导的基质细胞粘附激活
J Cell Sci. 2005 Jul 1;118(Pt 13):2965-74. doi: 10.1242/jcs.02411.

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