Abstract
An improved, rapid and inexpensive gel mobility shift assay was developed for the screening of anthracycline antibiotics. The assay based on the intercalation activity of these molecules into dsDNA was used to assess the activity of partially purified antibiotics. Detection limits were of 0.1 ng ml−1 with an average run time of 2 h. The assay is potentially useful for high throughput screening in bioprospecting, for monitoring fermentation production phases and downstream purification process.
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Amarante-Mendes GP, Green DR (1999) The regulation of apoptotic cell death. Brazil. J. Med. Biolog. Res. 32: 1053-1061.
Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C (1969a) Adriamycin, 14-hydroxydaunomycin, a new antitumor anti±iotic from S. peucetius var. caesius. Biotechnol. Bioeng. 11: 1101-1110.
Arcamone F, Franceschi G, Penco S (1969±) Adriamycin (14-hydroxydaunomycin), a novel antitumor anti±iotic. Tetrahedron Lett. 13: 1007-1010.
Arola JO, Saraste A, Pulkki K, Kalajoki M, Parvinen M, Voipio-Pulkki LM (2000) Acute doxorru±icin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res. 60: 1789-1792.
Chaires JB (1995) Molecular recognition of DNA ±y daunoru±icin. In: Prie±e W, ed. Anthracycline Anti±iotics. Washington, D.C.: American Chemical Society, pp. 156-167.
Culliname C, Rosmalen A, Phillips DR (1994) Does adriamycin induce interstrand crosslinks in DNA? Biochemistry 33: 4632-4638.
Cutts SM, Phillips DR (1995) Use of oligonucleotides to define the site of interstrand crosslinks induced ±y adriamycin. Nucl. Acids Res. 23: 2450-2456.
Di Marco A, Gaetani M, Orezzi P, Scarpinato BM, Silvestrini R, Soldati M, Dasdia T, Valentini L (1964) Daunomycin, a new anti±iotic of the rhodomycin group. Nature (London) 201: 706-707.
Doroshow JH (1995) Role of reactive-oxygen meta±olism in cardiac toxicity of anthracycline anti±iotics. In: Prie±e W, ed. Anthracycline Anti±iotics. Washington D.C.: American Chemical Society, pp. 259-267.
Drlica K, Franco RJ (1988) Inhi±itors of DNA topoisomerases. Biochemistry 27: 2253-2259.
Gewirtz DA (1999) A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline anti±iotics adriamycin and daunoru±icin. Biochem. Pharm. 57: 727-741.
Gi±±s JB, Oliff A, Kohl NE (1994) Farnesyl-transferase inhi±itors Ras reseach yields a potential cancer therapeutic. Cell 77: 175-178.
Hasels±erger K, Peterson DC, Thomas DG, Darling JL (1996) Assay of anticancer drugs in tissue culture: comparison of a tetrazolium-±ased assay and a protein ±inding dye assay in shortterm cultures derived from human malignant glioma. Anticancer Drugs 7: 331-338.
Horenstain MS, Heide RSV, L'Ecuyer,TJ (2000) Molecular ±asis of antracycline-induced cardiotoxicity and its prevention. Mol. Genet. Meta±. 71: 436-444.
Horto±ágyi GN (1997) Anthracyclines in the treatment of cancer. Drugs 54: 1-7.
Hotta K, Zhu CB, Phomsuwansiri P, Ishikida J, Mizuni S, Hatsu M, Imai S (1995) PCR inhi±ition assay for DNA targeted anti±iotics J. Anti±iotics 48: 1267-1272.
Kieser T, Bi±± MJ, Buttner MJ, Chater K.F, Hopwood DA (2000) Practical Streptomyces Genetics. Norwich, UK: The Johnn Innes Foundation.
Mendez C, Salas JA (2001) Altering the glycosilation pattern of ±ioactive compounds. Trends Biotechnol. 19: 449-456.
Mira±elli CK, Bartus H, Bartus JOL, Johnson R, Mong SM, Sung CP, Crooke ST (1985) Application of tissue culture microtitre test for the detection of antitumor agents. J. Anti±iotics 38: 758-766.
Mustonen P, Kinnunen PKJ (1993) On the reversal ±y deoxyri±onucleic acid of the ±inding of adriamycin to cardiolipin-containing liposomes. J. Biol. Chem. 268: 1074-1080.
Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C (1991) A rapid and simple method for measuring thymocyte apoptosis ±y propidium iodide staining and flow cytometry. J. Immunol. Meth. 139: 271-279.
Pommier Y (1995) DNA topoisomerases and their inhi±ition ±y anthracyclines. In: Prie±e W, ed. Anthracycline Anti±iotics. Washington D.C.: American Chemical Society, pp. 183-203.
Rosmalen A, Culliname C, Cutts SM, Phillips DR (1995) Sta±ility of adriamycin-induced DNA adducts and interstrand crosslinks. Nucl. Acids Res. 23: 42-50.
Shadle SE, Bammel BP, Cusack BJ, Knighton RA, Olson SJ, Mushlin PS, Olson RD (2000) Daunoru±icin cardiotoxicity. Evidence for the importance of the quinone moiety in a free-radical independent mechanism. Biochem. Pharm. 60: 1435-1444.
Shelton CJ, Harding MM, Prakash AS (1996) Enzymatic and chemical footprinting of anthracycline antitumor anti±iotics and related saccharide side chains. Biochemistry 35: 7974-7982.
Strohl WR, Bartel PL, Connors NC (1990) Biosynthesis of anthracyclines: analysis de mutantes de Streptomyces sp. strain C5 ±loked in daunomycin ±iosynthesis. J. Gen. Micro±iol. 136: 1877-1886.
Strohl WR, Dickens ML, Rajgarhia VB, Woo AJ, Priestley ND (1997) Antracyclines. In: Strohl WR, ed. Biotechnology of Anti±iotics. New York: M. Dekker, pp. 577-657. 1813
Wang JYT, Chao M, Wang AH-J (1995) Adducts of DNA and anthracycline anti±iotics: structures, interactions and activities. In: Prie±e W, ed. Anthracycline Anti±iotics. Washington D.C.: American Chemical Society, pp. 168-181.
Wang H, Mao Y, Zhou N, Hu T, Hsieh TS, Liu LF (2001) ATP±ound topoisomerase II as a target for antitumor drugs. J. Biol. Chem. 276: 15990-15995.
Zunino F, Pratesi G, Perego P (2001) Role of the sugar moiety in the pharmacological activity of anthracyclines: development of a novel series of disaccharide analogs. Biochem. Pharmacol. 61: 933-938.
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Furlan, R.L.A., Garrido, L.M., Brumatti, G. et al. A rapid and sensitive method for the screening of DNA intercalating antibiotics. Biotechnology Letters 24, 1807–1813 (2002). https://doi.org/10.1023/A:1020633909762
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DOI: https://doi.org/10.1023/A:1020633909762