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Design and utility of CCN2 anchor peptide aptamers.
Biochimie ( IF 3.3 ) Pub Date : 2010-05-04 , DOI: 10.1016/j.biochi.2010.04.021
Harumi Kawaki 1 , Satoshi Kubota , Eriko Aoyama , Naoya Fujita , Hiroshi Hanagata , Akira Miyauchi , Kenta Nakai , Masaharu Takigawa
Affiliation  

CCN family protein 2/connective tissue growth factor (CCN2/CTGF) consists of 4 conserved modules that are highly interactive with a number of biomolecules. With such interaction, CCN2 exerts multiple functions by forming an extracellular information network. In the present study, we screened for dodecapeptide sequences that bound to each module of human CCN2 by using a bacteriophage display library. Thereafter, consensus amino acid sequences for the binding to individual modules were extracted in silico and utilized to design anchor peptide aptamers that would facilitate the interaction between CCN2 and other molecules. Direct binding of a few peptides to CCN2 was confirmed by surface plasmon resonance analysis. Subsequent biological assay indicated that one such peptide was capable of promoting the proliferation of CCN2-producing chondrocytic cells. This cell biological activity was found to be sequence specific and CCN2 dependent. Since CCN2/CTGF was shown to be effective in articular cartilage/bone regeneration in vivo, utility of such peptide aptamers in CCN2-associated regenerative therapeutics is suggested herein.

中文翻译:

CCN2锚肽适体的设计和实用性。

CCN家族蛋白2 /结缔组织生长因子(CCN2 / CTGF)由与4个生物分子高度相互作用的4个保守模块组成。通过这种相互作用,CCN2通过形成细胞外信息网络发挥多种功能。在本研究中,我们通过使用噬菌体展示文库筛选了与人CCN2各个模块结合的十二肽序列。此后,以计算机方式提取用于结合各个模块的共有氨基酸序列,并用于设计锚定肽适体,该适体将促进CCN2与其他分子之间的相互作用。表面等离子体共振分析证实了一些肽与CCN2的直接结合。随后的生物学测定表明,一种这样的肽能够促进产生CCN2的软骨细胞的增殖。发现该细胞生物学活性是序列特异性的和CCN2依赖性的。由于显示CCN2 / CTGF在体内关节软骨/骨再生中是有效的,因此本文提出了这种肽适体在CCN2相关的再生治疗剂中的实用性。
更新日期:2010-04-30
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