Lexitropsine

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The name Lexitropsine describes a group of DNA -binding molecules that are analogues of the antibiotics netropsin and distamycin and can bind in the small groove of a DNA double strand .

properties

Some lexitropsins have antibacterial properties. Sequence-specific DNA alkylating agents were generated based on lexitropsins . Some of the alkylating agents have anti- tumor effects. Therefore, use of lexitropsins as chemotherapeutic agents has been investigated.

Depending on the structure of the lexitropsin, different DNA sequences are bound. They bind to an area of ​​four to six nucleotides . Some lexitropsins bind as dimers to the minor groove of their target DNA sequence in a head-to-tail orientation, ie two lexitropsins bind per double-stranded target sequence.

Selected representatives

Lexitropsine
Surname Lexitropsin A Lexitropsin B Lexitropsin C Lexitropsin D Lexitropsin E. Lexitropsin F Lexitropsin G
Structural formula Lexitropsins abc d.svg Lexitropsins ef g.svg
R 1 CH CH N N CH N N
R 2 CH N CH N N CH N

Individual evidence

  1. ↑ Sondhi SM, Praveen Reddy BS and Lown JW: Lexitropsin conjugates: Action on DNA targets . In: Current Medicinal Chemistry . 4, 1997, pp. 313-358.
  2. ^ Goodsell DS, Ng HL, Kopka ML, Lown JW, Dickerson RE: Structure of a dicationic monoimidazole lexitropsin bound to DNA . In: Biochemistry . 34, No. 51, 1995, pp. 16654-61. doi : 10.1021 / bi00051a013 . PMID 8527438 .
  3. ↑ NG Anthony, D. Breen, J. Clarke, G. Donoghue, AJ Drummond, EM Ellis, CG Gemmell, JJ Helesbeux, IS Hunter, AI Khalaf, SP Mackay, JA Parkinson, CJ Suckling, RD Waigh: Antimicrobial lexitropsins containing amide , amidines, and alkene linking groups. In: J Med Chem. (2007), Volume 50, Issue 24, pp. 6116-6125. PMID 17960927 .
  4. ^ WA Denny: DNA minor groove alkylating agents. In: Curr Med Chem. (2001), Volume 8, Issue 5, pp. 533-544. PMID 11281840 .
  5. ↑ MS Bobola, S. Varadarajan, NW Smith, RD Goff, DD Kolstoe, A. Blank, B. Gold, JR Silber: Human glioma cell sensitivity to the sequence-specific alkylating agent methyl-lexitropsin. In: Clinical Cancer Research . Volume 13, Number 2 Pt 1, January 2007, pp. 612-620, ISSN  1078-0432 . doi : 10.1158 / 1078-0432.CCR-06-1127 . PMID 17255284 . PDF .
  6. ↑ BS Reddy, SK Sharma, JW Lown: Recent developments in sequence selective minor groove DNA effectors. In: Current medicinal chemistry. Volume 8, Number 5, April 2001, pp. 475-508, ISSN  0929-8673 . PMID 11281837 .
  7. ↑ X. Han, C. Li, MD Mosher, KC Rider, P. Zhou, RL Crawford, W. Fusco, A. Paszczynski, NR Natale: Design, synthesis and biological evaluation of a novel class of anticancer agents: anthracenylisoxazole lexitropsin conjugates . In: Bioorganic & Medicinal Chemistry . Volume 17, Number 4, February 2009, pp. 1671-1680, ISSN  1464-3391 . doi : 10.1016 / j.bmc.2008.12.056 . PMID 19167892 . PMC 2978248 (free full text).
  8. ^ Goodsell DS: Sequence recognition of DNA by lexitropsins . In: Curr Med Chem . 8, No. 5, 2001, pp. 509-16. PMID 11281838 .
  9. ^ A b N. G. Anthony, KR Fox, BF Johnston, AI Khalaf, SP Mackay, IS McGroarty, JA Parkinson, GG Skellern, CJ Suckling, RD Waigh: DNA binding of a short lexitropsin. In: Bioorg Med Chem Lett. (2004), Volume 14, Issue 5, pp. 1353-1356. PMID 14980697 .