Netropsin

Netropsin (also termed congocidine or sinanomycin[1]) is a polyamide with antibiotic and antiviral activity. Netropsin was discovered by Finlay et al., and first isolated from the actinobacterium Streptomyces netropsis.[2] It belongs to the class of pyrrole-amidine antibiotics.

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
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.162.288
PubChem CID
UNII
InChI
  • InChI=1S/C18H26N10O3/c1-27-9-11(6-12(27)16(30)23-4-3-14(19)20)26-17(31)13-5-10(8-28(13)2)25-15(29)7-24-18(21)22/h5-6,8-9H,3-4,7H2,1-2H3,(H3,19,20)(H,23,30)(H,25,29)(H,26,31)(H4,21,22,24) N
    Key: IDBIFFKSXLYUOT-UHFFFAOYSA-N N
  • InChI=1/C18H26N10O3/c1-27-9-11(6-12(27)16(30)23-4-3-14(19)20)26-17(31)13-5-10(8-28(13)2)25-15(29)7-24-18(21)22/h5-6,8-9H,3-4,7H2,1-2H3,(H3,19,20)(H,23,30)(H,25,29)(H,26,31)(H4,21,22,24)
    Key: IDBIFFKSXLYUOT-UHFFFAOYAW
SMILES
  • [H]/N=C(/CCNC(=O)c1cc(cn1C)NC(=O)c2cc(cn2C)NC(=O)CN=C(N)N)\N
Properties
Chemical formula
 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 YN ?)
Infobox references

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] Thus, 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 on single molecules 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
  • Lexitropsin
  • Hoechst 33258
  • DAPI
  • Pentamidine
  • DNA-binding protein
  • Single-strand binding protein
  • Comparison of nucleic acid simulation software

References
  1. Netropsin dihydrochloride at Sigma-Aldrich
  2. A.C. Finlay, F. A. Hochstein, B. A. Sobin, and F. X. Murphy, J. Am. Chem Soc. 73 341-343 (1951)
  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)
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