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钙卫蛋白聚乙二醇化增强了其物理和结构性质。

Calprotectin Pegylation Enhanced Its Physical and Structural Properties.

作者信息

Shahsavari Abbas, Azad Mehdi, Mobarra Naser, Chegini Koorosh Goodarzvand, Gheibi Nematollah

机构信息

Department of Biotechnology, Paramedical School, Qazvin University of Medical Sciences, Qazvin, Iran.

Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

出版信息

Protein J. 2016 Oct;35(5):363-370. doi: 10.1007/s10930-016-9680-z.

Abstract

Calprotectin is member of the S-100 protein family with a wide plethora of intra-and extracellular functions. Anticancer activities, antimicrobial effects and being a qualified disease marker are among the compelling features of this protein to be used as a pharmaceutical agent. However, there are several impediments to applications of protein pharmaceuticals including: proteolytic degradation, short circulating half-life, low solubility and immunogenicity. Pegylation is a common bioconjugation polymer capable of overcoming these drawbacks. Recombinant expression and purification of calprotectin along with its pegylation would result in enhanced pharmaco-dynamic and pharmacokinetic properties. Our florescence spectroscopy and far Ultraviolet-optical density results indicate that pegylation altered the physical and structural properties of the calprotectin to become in a more stable and functionally active state. Due to enhanced pharmacodynamic and pharmacokinetic properties of the calprotectin via pegylation, this study would pave the way for better in vitro and in vivo validations of calprotectin applications in medical practice.

摘要

钙卫蛋白是S-100蛋白家族的成员,具有广泛的细胞内和细胞外功能。抗癌活性、抗菌作用以及作为一种合格的疾病标志物是这种蛋白质用作药物的引人注目的特性。然而,蛋白质药物的应用存在若干障碍,包括:蛋白水解降解、循环半衰期短、溶解度低和免疫原性。聚乙二醇化是一种能够克服这些缺点的常见生物共轭聚合物。钙卫蛋白的重组表达、纯化及其聚乙二醇化将导致药效学和药代动力学性质增强。我们的荧光光谱和远紫外光密度结果表明,聚乙二醇化改变了钙卫蛋白的物理和结构性质,使其处于更稳定和功能活跃的状态。由于通过聚乙二醇化增强了钙卫蛋白的药效学和药代动力学性质,本研究将为钙卫蛋白在医学实践中的应用进行更好的体外和体内验证铺平道路。

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