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Netropsin
ββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββ
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Netropsin ist ein Polyamid-Antibiotikum, das an die kleine Furche einer DNA-Doppelhelix bindet.cite-ref-2[2] Es wirkt gegen Gram-positive und Gram-negative Bakterien.cite-ref-3[3]
Contents
β’ Eigenschaften
β’ Einzelnachweise
ββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββββ
Eigenschaften
Netropsin wurde erstmals 1951 durch A. C. Finlay beschrieben, der es aus dem Actinobakterium Streptomyces netropsis isoliert hatte.cite-ref-4[4] Netropsin gehΓΆrt zur Klasse Pyrrol-Amidin-Antibiotika und ist ein Analogon von Distamycin und den Lexitropsinen. Es bindet bevorzugt AT-reiche DNA-Sequenzen doppelstrΓ€ngiger DNA und Tetraden aus [TGGGGT]4,cite-ref-5[5]cite-ref-6[6]cite-ref-7[7] nicht jedoch an einzelstrΓ€ngige DNA oder RNA. Die Bindung von Netropsin fΓΌhrt zu einer engeren Windung von etwa 9Β° pro gebundenem Lexitropsin und Basenpaar.cite-ref-8[8]cite-ref-9[9] Bei einer positiven Superspiralisierung entspannt es daher die DNA, wΓ€hrend es eine negative Superspiralisierung verstΓ€rkt.cite-ref-10[10] Der Bindungsmechanismus ist noch nicht vollstΓ€ndig geklΓ€rt.cite-ref-11[11] Verschiedene Distamycin-Derivate wurden entwickelt, um als Alkylanzien gegen Tumoren eingesetzt zu werden oder zur Fluoreszenzmarkierung von doppelstrΓ€ngiger DNA.cite-ref-12[12]cite-ref-13[13]cite-ref-14[14]
Einzelnachweise
cite-note-sigma-11. Datenblatt Netropsin dihydrochloride bei Sigma-Aldrich, abgerufen am 24. November 2013 (PDF).
cite-note-22. β M. P. Barrett, C. G. Gemmell, C. J. Suckling: Minor groove binders as anti-infective agents. In: Pharmacology & Therapeutics. Band 139, Nummer 1, Juli 2013, S. 12β23, doi:10.1016/j.pharmthera.2013.03.002. PMID 23507040.
cite-note-33. β C. Zimmer, U. WΓ€hnert: Nonintercalating DNA-binding ligands: specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material. In: Progress in biophysics and molecular biology. Band 47, Nummer 1, 1986, S. 31β112, PMID 2422697.
cite-note-44. β A.C. Finlay, F. A. Hochstein, B. A. Sobin, and F. X. Murphy, J. Am. Chem. Soc. 73 341β343 (1951). doi:10.1021/ja01145a113.
cite-note-55. β M. L. Kopka, C. Yoon, D. Goodsell, P. Pjura, and R.E. Dickerson, J. Mol. Biol. 183 553β563 (1985)
cite-note-66. β M. L. Kopka, C. Yoon, D. Goodsell, P. Pjura, R. E. Dickerson: The molecular origin of DNA-drug specificity in netropsin and distamycin. In: Proceedings of the National Academy of Sciences of the United States of America. Band 82, Nummer 5, MΓ€rz 1985, S. 1376β1380, PMID 2983343. PMC 397264 (freier Volltext).
cite-note-77. β B. Pagano, I. Fotticchia, S. De Tito, C. A. Mattia, L. Mayol, E. Novellino, A. Randazzo, C. Giancola: Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)](4). In: Journal of nucleic acids. Band 2010, doi:10.4061/2010/247137. PMID 20725616. PMC 2915651 (freier Volltext).
cite-note-88. β G. Snounou and A. D. B. Malcolm, J. Mol. Biol. 167 211β216 (1983)
cite-note-99. β H. Triebel, H. BΓ€r, R. Geuther, and G. Burckhardt, Progr. Colloid. Polym. Sci. 99 45β54 (1995).
cite-note-1010. β J. Lipfert, S. Klijnhout, N. H. Dekker: Torsional sensing of small-molecule binding using magnetic tweezers. In: Nucleic Acids Research. Band 38, Nummer 20, November 2010, S. 7122β7132, doi:10.1093/nar/gkq598. PMID 20624816. PMC 2978369 (freier Volltext).
cite-note-1111. β Y. Y. Fang, V. R. Morris, G. M. Lingani, E. C. Long, W. M. Southerland: Genome-Targeted Drug Design: Understanding the Netropsin-DNA Interaction. In: The open conference proceedings journal. Band 1, 2010, S. 157β163, PMID 21297883. PMC 3032215 (freier Volltext).
cite-note-1313. β C. Bailly, J. B. Chaires: Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues. In: Bioconjugate Chemistry. Band 9, Nummer 5, 1998 Sep-Oct, S. 513β538, doi:10.1021/bc980008m. PMID 9736486.
cite-note-1414. β T. Vaijayanthi, T. Bando, G. N. Pandian, H. Sugiyama: Progress and prospects of pyrrole-imidazole polyamide-fluorophore conjugates as sequence-selective DNA probes. In: ChemBioChem Band 13, Nummer 15, Oktober 2012, S. 2170β2185, doi:10.1002/cbic.201200451. PMID 23023993.