Netropsin

Netropsin
Names
IUPAC name
N-{5-[(3-Amino-3-iminopropyl)carbamoyl]-1-methyl-1H-pyrrol-3-yl}-4-[(N-carbamimidoylglycyl)amino]-1-methyl-1H-pyrrole-2-carboxamide
Other names
Nt, congocidin, sinanomycin
Identifiers
1438-30-8 YesY
ChEMBL ChEMBL553984 N
ChemSpider 4306 N
Jmol interactive 3D Image
PubChem 4461
Properties
C18H26N10O3 · 2HCl
Molar mass 503.39 g/mol
Appearance White powder
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Netropsin is a polyamide with antibiotic and antiviral activity. Netropsin was discovered by Finlay et al. and first isolated from the actinobacterium Streptomyces netropsis.[1] It belongs to the class of pyrrole-amidine antibiotics. Synonyms for the compound are congocidine and sinanomycin.[2]

DNA binding properties

Netropsin binds to the minor groove of AT-rich sequences of double stranded DNA.[3] In contrast, netropsin does not bind single stranded DNA or double stranded RNA. Crystallographic structures of DNA-bound Netropsin have been obtained and elucidate details of how the drug binds in the minor groove.[4][5] In the bound structure, the drug makes hydrogen bonding interactions with four subsequent base pairs of the DNA duplex, locally displacing the water molecules of the spine of hydration.

Netropsin (shown in space-filling representation) bound to DNA (shown as bonds)

Using gel mobility and analytical ultracentrifugation, it was shown that Netropsin binding to DNA increases the twist per base by similar to 9˚ per molecule bound.[6][7] Therefore, it removes supercoils when interacting with positively supercoiled DNA and introduces (additional) negative supercoils when binding to relaxed or negatively supercoiled DNA. Netropsin's effect on supercoiled DNA was observed in detail at the single-molecule level using a magnetic tweezers.[8]

Antibiotic properties

It has been shown that Netropsin is active both against Gram-positive bacteria and Gram-negative bacteria .[9]

See also

References

  1. ↑ A.C. Finlay, F. A. Hochstein, B. A. Sobin, and F. X. Murphy, J. Am. Chem Soc. 73 341-343 (1951)
  2. ↑ Netropsin dihydrochloride at Sigma-Aldrich
  3. ↑ C. Zimmer and U. Wähnert, Prog. Biophys. Molec. Biol. 47 31-112 (1986)
  4. ↑ M. L. Kopka, C. Yoon, D. Goodsell, P. Pjura, and R.E. Dickerson, J. Mol. Biol. 183 553-563 (1985)
  5. ↑ M. L. Kopka, C. Yoon, D. Goodsell, P. Pjura, and R.E. Dickerson, Proc. Natl. Acad. Sci. USA 82 1376-1380 (1985)
  6. ↑ G. Snounou and A. D. B. Malcolm, J. Mol. Biol. 167 211-216 (1983)
  7. ↑ H. Triebel, H. Bär, R. Geuther, and G. Burckhardt, Progr. Colloid. Polym. Sci. 99 45-54 (1995)
  8. ↑ J. Lipfert, S. Klijnhout, and Nynke H. Dekker, "Nucleic Acids Res." "38" 7122-32 (2010)
  9. ↑ C. Zimmer and U. Wähnert, Prog. Biophys. Molec. Biol. 47 31-112 (1986)
This article is issued from Wikipedia - version of the Thursday, March 03, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.