|
|
- 2016
一种基于小分子多肽配体检测AD7c-NTP的新方法
|
Abstract:
摘要： 与阿尔兹海默症相关的神经纤维蛋白(AD7c-NTP)是目前被广泛关注的一种用于早期诊断阿尔兹海默症的标志物,该标志物具有易获得、无创性的检测优势。本研究目的是检测尿液中的阿尔兹海默症标志物AD7c-NTP。通过分子模拟设计小分子多肽配体,固相合成方法合成多肽,基因克隆、原核表达AD7c-NTP,采用色谱方法分析小分子多肽配体的吸附能力、AD7c-NTP的检测范围以及在模拟尿液中的吸附情况。研究设计的DEWH配体可以与AD7c-NTP特异性结合,并且结合率达到了85%,该方法检测的线性范围是200~900 μg/L。该研究提供了一种便携的、可重复检测AD7c-NTP的方法,为阿尔兹海默早期诊断及延缓疾病奠定基础。
Abstract: Alzheimer-associated neuronal thread protein(AD7c-NTP)as a sensitive, easily obtained and noninvasive biomarker for AD disease detection. This research is aim to detect AD7c-NTP protein. A novel peptide for detecting AD7c-NTP was developed using molecular simulations and the peptide was synthesized. The recombinant protein was expressed. The bound protein was tested using chromatography and the mimic urine was detected as well. The peptide of DEWH is able to bind AD7c-NTP with the adsorption rate of around 85% and the linearity range is 200-900 μg/L. This novel peptide could provide an easy and repeatable method for detecting AD disease, which is critical for early diagnosis and postponing disease progression with proper treatment
| [1] | LIPMAN N S, JACKSON L R, TRUDEL L J, et al. Monoclonal versus polyclonal antibodies: distinguishing characteristics, applications, and information resources[J]. ILAR Journal, 2005, 46(3):258-268. |
| [2] | YANG J, YAN R, ROY A, et al. The I-TASSER Suite: protein structure and function prediction[J]. Nature Methods, 2015, 12(1):7-8. |
| [3] | MONTE S M, GHANBARI K, FREY W H, et al. Characterization of the AD7C-NTP cDNA expression in Alzheimers disease and measurement of a 41-kD protein in cerebrospinal fluid[J]. Journal of Clinical Investigation, 1997, 100(12):3093-3104. |
| [4] | WEI Y P, XU J D, ZHANG L, et al. Development of novel small peptide ligands for antibody purification[J]. RSC Advances, 2015, 5(82):67093-67096. |
| [5] | ZHANG J, SHI S L. A literature review of AD7c-ntp as a biomarker for Alzheimers disease[J]. Annals of Indian Academy Neurology, 2013, 16(3):307-319. |
| [6] | YOUN Y C, PARK K W, HAN S H, et al. Urine neural thread protein measurements in Alzheimer disease[J]. Journal of the American Medical Directors Association, 2011, 12(5):372-376. |
| [7] | LEVY S, MCCONVILLE M, LAZARO G A, et al. Competitive ELISA studies of neural thread protein in urine in Alzheimers disease[J]. Journal of Clinical Laboratory Analysis, 2007, 21(1):24-33. |
| [8] | ROY A, KUCUKURAL A, ZHANG Y. I-TASSER: a unified platform for automated protein structure and function prediction[J]. Nature Protocols, 2010, 5(4):725-738. |
| [9] | ZHANG Y. I-TASSER server for protein 3D structure prediction[J]. BMC bioinformatics, 2008, 9(1):40-47. |
| [10] | LUKENS J N, VAN DEERLIN V, CLARK C M, et al. Comparisons of telomere lengths in peripheral blood and cerebellum in Alzheimers disease[J]. Alzheimers & Dementia, 2009, 5(6):463-469. |
| [11] | MONTE S M, WANDS J R. The AD7c-NTP neuronal thread protein biomarker for detecting Alzheimers disease[J]. Journal of Alzheimers Disease, 2001, 3(3):345-353. |
| [12] | WANG C, CUI Y, YANG J, et al. Combining serum and urine biomarkers in the early diagnosis of mild cognitive impairment that evolves into Alzheimers disease in patients with the apolipoprotein E ε4 genotype[J]. Biomarkers, 2015, 20(1):84-88. |
| [13] | GOODMAN I, GOLDEN G, FLITMAN S, et al. A multi-center blinded prospective study of urine neural thread protein measurements in patients with suspected Alzheimers disease[J]. Journal of the American Medical Directors Association, 2007, 8(1):21-30. |
| [14] | Alzheimers Association. 2015 Alzheimers disease facts and figures[J]. Alzheimers & Dementia, 2015, 11(3):332-384. |
| [15] | SORENSEN A A. Alzheimers disease research: scientific productivity and impact of the top 100 investigators in the field[J]. Journal of Alzheimers Disease, 2009, 16(3):451-465. |
| [16] | MA L, CHEN J, WANG R, et al. The level of Alzheimer-associated neuronal thread protein in urine may be an important biomarker of mild cognitive impairment[J]. Journal of Clinical Neuroscience, 2015, 22(4):649-652. |
