Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Recognition between mitomycin C and specific DNA sequences for cross-link formation.

H Borowy-Borowski1, R Lipman, M Tomasz

  • 1Department of Chemistry, Hunter College, City University of New York, New York 10021.

Biochemistry
|March 27, 1990
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Role of mitochondria in neuronal cell death induced by oxidative stress; neuroprotection by Coenzyme Q10.

Neurobiology of disease·2005
Same author

Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10.

Toxicology and applied pharmacology·2004
Same author

Reductive activation of mitomycin A by thiols.

Organic letters·2001
Same author

Solution structure of a guanine-N7-linked complex of the mitomycin C metabolite 2,7-diaminomitosene and DNA. Basis of sequence selectivity.

Biochemistry·2001
Same author

Selective activation of mitomycin A by thiols to form DNA cross-links and monoadducts: biochemical basis for the modulation of mitomycin cytotoxicity by the quinone redox potential.

Journal of medicinal chemistry·2001
Same author

Bioreductive metabolism of mitomycin C in EMT6 mouse mammary tumor cells: cytotoxic and non-cytotoxic pathways, leading to different types of DNA adducts. The effect of dicumarol.

Biochemical pharmacology·2001

Mitomycin C (MC) cross-linking of DNA is highly specific for the CG.CG duplex sequence, with reactivity influenced by base pairing and minor groove interactions. This specificity is crucial for understanding drug-DNA binding and developing targeted therapies.

Area of Science:

  • Molecular Biology
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Mitomycin C (MC) is an antitumor antibiotic that functions as a DNA cross-linking agent.
  • Understanding the sequence specificity of MC-induced DNA cross-linking is critical for its therapeutic application.
  • Previous studies suggested sequence preferences, but the precise requirements remained to be elucidated.

Purpose of the Study:

  • To extensively investigate the sequence requirements for mitomycin C (MC) induced DNA cross-linking.
  • To characterize the structure of MC-oligonucleotide adducts and determine the yield of cross-linked products.
  • To elucidate the mechanistic basis for MC's sequence specificity in DNA binding.

Main Methods:

  • Synthesis and reaction of a series of oligodeoxyribonucleotides with reductively activated mitomycin C (MC).

Related Experiment Videos

  • Isolation and characterization of cross-linked drug-oligonucleotide complexes using reverse-phase HPLC.
  • Nucleoside and MC-nucleoside adduct analysis to quantify cross-linking efficiency and identify adducts.

    • Main Results:

    • High yields of cross-links were observed specifically between guanines in CG.CG duplex sequences.
    • GC.GC, CGC.GCG, and CGC.ICG sequences showed significantly reduced or no cross-linking.
    • A four-base-pair sequence preference (PuCGPyr.PuCGPyr) was identified, with GpPyr being more reactive than GpPu.

    Conclusions:

    • Mitomycin C (MC) cross-linking exhibits absolute specificity for the CG.CG duplex sequence.
    • The observed specificity is attributed to the precise orientation of monofunctionally bound MC within the DNA minor groove.
    • Sequence context, particularly the pyrimidine base adjacent to guanine, influences MC reactivity, guiding future drug design.