Netropsin

Structural formula
General
Surname	Netropsin
other names	Nt; Congocidin; Sinanomycin;
Molecular formula	C 18 H 26 N 10 O 3 • 2HCl
Brief description	yellow solid
External identifiers / databases
EC number	634-294-2
ECHA InfoCard	100.162.288
PubChem	4461
Wikidata	Q3874969
properties
Molar mass	503.39 g mol −1
Physical state	firmly
Melting point	> 300 ° C
safety instructions
GHS labeling of hazardous substances
H and P phrases	H: 301
	P: 301-310
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Netropsin is a polyamide - antibiotic that to the minor groove of DNA - the double helix binds. It works against gram-positive and gram-negative bacteria .

properties

Netropsin bound to DNA. From PDB 101D.

Netropsin was first described in 1951 by AC Finlay, who isolated it from the actinobacterium Streptomyces netropsis . Netropsin belongs to the class pyrrole - amidine antibiotics and is an analogue of distamycin and the lexitropsins . It preferentially binds AT-rich DNA sequences of double-stranded DNA and tetrads from [TGGGGT] ₄ , but not to single-stranded DNA or RNA . The binding of netropsin leads to a tighter turn of about 9 ° per bound lexitropsin and base pair. Therefore, when the supercoiling is positive , it relaxes the DNA, while it is increasing a negative supercoiling. The binding mechanism is not yet fully understood. Various distamycin derivatives have been developed to be used as alkylating agents against tumors or for fluorescent labeling of double-stranded DNA.

Individual evidence

↑ ^a ^b ^c ^d ^e data sheet Netropsin dihydrochloride from Sigma-Aldrich , accessed on November 24, 2013 ( PDF ).
↑ MP Barrett, CG Gemmell, CJ Suckling: Minor groove binders as anti-infective agents. In: Pharmacology & Therapeutics . Volume 139, number 1, July 2013, pp. 12-23, doi : 10.1016 / j.pharmthera.2013.03.002 . PMID 23507040 .
↑ C. Zimmer, U. Wähnert: 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. Volume 47, Number 1, 1986, pp. 31-112, PMID 2422697 .
↑ AC Finlay, FA Hochstein, BA Sobin, and FX Murphy, J. Am. Chem. Soc. 73 341-343 (1951). doi : 10.1021 / ja01145a113 .
↑ ML Kopka, C. Yoon, D. Goodsell, P. Pjura, and RE Dickerson, J. Mol. Biol. 183 553-563 (1985)
↑ ML Kopka, C. Yoon, D. Goodsell, P. Pjura, RE 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 . Volume 82, Number 5, March 1985, pp. 1376-1380, PMID 2983343 . PMC 397264 (free full text).
↑ B. Pagano, I. Fotticchia, S. De Tito, CA 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. Volume 2010, 2010, S., doi : 10.4061 / 2010/247137 . PMID 20725616 . PMC 2915651 (free full text).
↑ G. Snounou and ADB Malcolm, J. Mol. Biol. 167 211-216 (1983)
↑ H. Triebel, H. Bär, R. Geuther, and G. Burckhardt, Progr. Colloid. Polym. Sci. 99 45-54 (1995).
↑ J. Lipfert, p Klijnhout, NH Dekker: Torsional sensing of small-molecule binding using magnetic tweezers. In: Nucleic Acids Research . Volume 38, Number 20, November 2010, pp. 7122-7132, doi : 10.1093 / nar / gkq598 . PMID 20624816 . PMC 2978369 (free full text).
↑ YY Fang, VR Morris, GM Lingani, EC Long, WM Southerland: Genome-Targeted Drug Design: Understanding the Netropsin-DNA Interaction. In: The open conference proceedings journal. Volume 1, 2010, pp. 157-163, PMID 21297883 . PMC 3032215 (free full text).
↑ GS Khan, A. Shah, Zia-ur-Rehman, D. Ba: Chemistry of DNA minor groove binding agents. In: Journal of photochemistry and photobiology. B, Biology. Volume 115, October 2012, pp. 105-118, doi : 10.1016 / j.jphotobiol.2012.07.003 . PMID 22857824 .
↑ C. Bailly, JB Chaires: Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues. In: Bioconjugate Chemistry . Volume 9, Number 5, 1998 Sep-Oct, pp. 513-538, doi : 10.1021 / bc980008m . PMID 9736486 .
↑ T. Vaijayanthi, T. Bando, GN Pandian, H. Sugiyama: Progress and prospects of pyrrole-imidazole polyamide-fluorophore conjugates as sequence-selective DNA probes. In: ChemBioChem Volume 13, Number 15, October 2012, pp. 2170-2185, doi : 10.1002 / cbic.201200451 . PMID 23023993 .

[Sigma-1] ↑ ^a ^b ^c ^d ^e data sheet Netropsin dihydrochloride from Sigma-Aldrich , accessed on November 24, 2013 ( PDF ).

[2] MP Barrett, CG Gemmell, CJ Suckling: Minor groove binders as anti-infective agents. In: Pharmacology & Therapeutics . Volume 139, number 1, July 2013, pp. 12-23, doi : 10.1016 / j.pharmthera.2013.03.002 . PMID 23507040 .

[3] C. Zimmer, U. Wähnert: 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. Volume 47, Number 1, 1986, pp. 31-112, PMID 2422697 .

[4] AC Finlay, FA Hochstein, BA Sobin, and FX Murphy, J. Am. Chem. Soc. 73 341-343 (1951). doi : 10.1021 / ja01145a113 .

[5] ML Kopka, C. Yoon, D. Goodsell, P. Pjura, and RE Dickerson, J. Mol. Biol. 183 553-563 (1985)

[6] ML Kopka, C. Yoon, D. Goodsell, P. Pjura, RE 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 . Volume 82, Number 5, March 1985, pp. 1376-1380, PMID 2983343 . PMC 397264 (free full text).

[7] B. Pagano, I. Fotticchia, S. De Tito, CA 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. Volume 2010, 2010, S., doi : 10.4061 / 2010/247137 . PMID 20725616 . PMC 2915651 (free full text).

[8] G. Snounou and ADB Malcolm, J. Mol. Biol. 167 211-216 (1983)

[9] H. Triebel, H. Bär, R. Geuther, and G. Burckhardt, Progr. Colloid. Polym. Sci. 99 45-54 (1995).

[10] J. Lipfert, p Klijnhout, NH Dekker: Torsional sensing of small-molecule binding using magnetic tweezers. In: Nucleic Acids Research . Volume 38, Number 20, November 2010, pp. 7122-7132, doi : 10.1093 / nar / gkq598 . PMID 20624816 . PMC 2978369 (free full text).

[11] YY Fang, VR Morris, GM Lingani, EC Long, WM Southerland: Genome-Targeted Drug Design: Understanding the Netropsin-DNA Interaction. In: The open conference proceedings journal. Volume 1, 2010, pp. 157-163, PMID 21297883 . PMC 3032215 (free full text).

[12] GS Khan, A. Shah, Zia-ur-Rehman, D. Ba: Chemistry of DNA minor groove binding agents. In: Journal of photochemistry and photobiology. B, Biology. Volume 115, October 2012, pp. 105-118, doi : 10.1016 / j.jphotobiol.2012.07.003 . PMID 22857824 .

[13] C. Bailly, JB Chaires: Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues. In: Bioconjugate Chemistry . Volume 9, Number 5, 1998 Sep-Oct, pp. 513-538, doi : 10.1021 / bc980008m . PMID 9736486 .

[14] T. Vaijayanthi, T. Bando, GN Pandian, H. Sugiyama: Progress and prospects of pyrrole-imidazole polyamide-fluorophore conjugates as sequence-selective DNA probes. In: ChemBioChem Volume 13, Number 15, October 2012, pp. 2170-2185, doi : 10.1002 / cbic.201200451 . PMID 23023993 .