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Journal of Zhejiang University SCIENCE A 2004 Vol.5 No.8 P.900-905

http://doi.org/10.1631/jzus.2004.0900


Affinity ultrafiltration of DNA topoisomerases-targeted compounds determined with HPLC/ESI-MS for drug candidate screening


Author(s):  ZHANG Hong, PAN Yuan-jiang

Affiliation(s):  Department of Chemistry, Zhejiang University, Hangzhou 310027, China; more

Corresponding email(s):   panyuanjiang@css.zju.edu.cn

Key Words:  Affinity, High-throughput screening, LC-MS, Topoisomerase, Ultrafiltration


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ZHANG Hong, PAN Yuan-jiang. Affinity ultrafiltration of DNA topoisomerases-targeted compounds determined with HPLC/ESI-MS for drug candidate screening[J]. Journal of Zhejiang University Science A, 2004, 5(8): 900-905.

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T1 - Affinity ultrafiltration of DNA topoisomerases-targeted compounds determined with HPLC/ESI-MS for drug candidate screening
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A1 - PAN Yuan-jiang
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DOI - 10.1631/jzus.2004.0900


Abstract: 
A method of screening assay is demonstrated. The approach is based on the affinity of antitumor candidates for topoi-somerases. In this method, antitumor candidates are fished out using topoisomerases as targets. Traditional analysis of complex compounds typically encounters signal suppression due to the relatively low concentrations, but enzyme-affinity screening for the active compounds can effectively concentrate the desired analysts into a small volume of high concentration. Active compounds are separated from non-affinity compounds by ultrafiltration. The molecules-enzymes complexes that are retained on the filter are subsequently separated by acidification to obtain the topoisomerases-affinity compounds for analysis on High Performance Liquid Chromatography coupled with electrospray ionization mass spectrometric detection (ESI-MS). This enzyme-affinity based screening assay provides a highly specific and efficient method that can directly screen, identify, and acquire drug candidates thus improving the accuracy and speed of high-throughput screening activities.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1] Bjergbaek, L., Kingma, P., Nielsen, I.S., Wang, Y., Werstergaard, O., Osheroff, N., Andersen, A.H., 2000. Communication between the ATPase and cleavage/religation domains of human topoisomerase II alpha. J Biol Chem, 275:13041-13048.

[2] Brimmel, C.L., Vickennan, J.C., Cart, S.A., 1996. Evaluation of mass spectrometric methods applicable to the direct analysis of non-peptide beed-bound combinatorial libraries. Anal Chem, 68:237-242.

[3] Burbaum, J., 1998. Miniaturization technologic in HTS: how fast, how small, how soon. Drug Discovery Today, 3:313-322.

[4] Chang, J.Y., Dethlefsen, L.A., Barley, L.R., Zhou, B.S., Cheng, Y.S., 1992. Characterization of camptothecin resistant Chinese hamster lung cells. Biochem Pharmacology, 43:2443-2452.

[5] De Isabella, P., Capranico, G., Binaschi, M., Tinelli, S., Zunino, F., 1990. Evidence of topoisomerase II-dependent mechanisms of multidrug resistance in p388 leukemia cells. Mol. Pharmacol, 37:11.

[6] Froelich, A.S.J., Osheroff, N., 1995. Topoisomerase poisons: harnessing the dark side of enzyme mechanism. J Biol Chem, 270:21429-21432.

[7] Gund, P., Nolan, H.S., 1999. Applying informatics systems to high-throughput screening and analysis. Phamainformatics, 1:25-29.

[8] Hengel, A.J.V., Harkes, M.P., Wichers, H.J., 1992. Characterization of callus formation and camptothecin production by cell lines of Camptotheca acuminate. Plant Cell, Tissue and Organ Culture, 28:11-18.

[9] Husain, I., Mohler, J.L., Siegler, H.F., Besterman, J.M., 1994. Elevation of topoisomerase I messenger RNA, protein, and catalytic activity in human tumors: demonstration of tumor-type specificity and implications for cancer chemotherapy. Cancer Research, 54:539-546.

[10] Kaufmann, S.H., Charron, M., Burke, P.J., Karp, J.E., 1995. Changes in topoisomerase I levels and localization during myeloid maturation in vitro and in vivo. Cancer Research, 55:1255-1260.

[11] Liu, X., 1992. Study on anti-tumors drugs which affect on DNA topoisomerases. Oversea Medical Science, 19:201-205 (in Chinese).

[12] Li, Y.Y., Li, Z.Y., Wang, H., You, Q.D., 1996. DNA topoisomerases and anticancer drugs. Pharmic Advance, 20:138-142 (in Chinese).

[13] Major, J., 1998. Challenges and opportunities in high throughput screening: implication for new technologies. J Biomol Screening, 3:13-17.

[14] Meng, L.H., Zhang, J.S., Ding, J., 2001. Salvicine, a novel DNA topoisomerase II inhibitor, exerting its effects by trapping enzyme-DNA cleavage complexes. Biochem. Pharmaco., 62:733-741.

[15] Sundberg, S.A., 2000. High-throughput and ultra-high throughput screening: solution- and cell-based approaches. Current Opinion in Biotechnology, 11:47-53.

[16] Wang, J.C., 1996. DNA Topoisomerases. Annu Rev Biochem, 65:635-692.

[17] Wang, Y., Thyssen, A., Westergaard, O., Andersen, A.H., 2000. Position-specific effect of ribonucleotides on the cleavage activity of human topoisomerase II. Nucleic Acids Res, 28:4815-4821.

[18] Wiehodt, R., Zweigenbaum, J., Henion, J., 1997. Immunoaffinity ultrafiltration with ion spray HPLC/Ms for screening small-molecule libraries. Anal Chem, 69:1683-1691.

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