The unifying mechanism of bioactivity in all enediyne antibiotics is the Bergman cyclization, wherein the enediyne portion undergoes spontaneous cycloaromatization to generate a para-benzyne biradical activated toward homolytic abstraction of hydrogen from suitable donors, including the deoxyribose sugars of DNA.
This generates a carbon-centered free radical on DNA, which undergoes oxidation by molecular oxygen.
The resulting peroxide decomposes to form single- or double-stranded breaks in DNA, ultimately leading to cell death.

With considerable sequence selectivity, kedarcidin chromophore binds and cleaves DNA preferentially at TCCTn-mer sites, producing single-strand breaks.
Puzzlingly, while the structure of kedarcidin chromophore is most closely related to that of neocarzinostatin chromophore, the former shares sequence-specificity with the structurally distinct calicheamicin enediyne antitumor antibiotic.
The naphthoic acid substructure has been implicated in DNA binding, likely through intercalation.
To this end, kedarcidin chromophore–induced DNA cleavage is diminished by the addition of divalent cations such as Ca²⁺ and Mg²⁺, which chelatively bind the naphthoic acid group of kedarcidin chromophore and thus lessen its affinity for DNA.
Competition experiments with netropsin, a known binder of the DNA minor groove, indicate that kedarcidin likely binds the minor groove as well.
The unifying mechanism of bioactivity in all enediyne antibiotics is the Bergman cyclization, wherein the enediyne portion undergoes spontaneous cycloaromatization to generate a para-benzyne biradical activated toward homolytic abstraction of hydrogen from suitable donors, including the deoxyribose sugars of DNA. This generates a carbon-centered free radical on DNA, which undergoes oxidation by molecular oxygen. The resulting peroxide decomposes to form single- or double-stranded breaks in DNA, ultimately leading to cell death.
With considerable sequence selectivity, kedarcidin chromophore binds and cleaves DNA preferentially at TCCTn-mer sites, producing single-strand breaks. Puzzlingly, while the structure of kedarcidin chromophore is most closely related to that of neocarzinostatin chromophore, the former shares sequence-specificity with the structurally distinct calicheamicin enediyne antitumor antibiotic. The naphthoic acid substructure has been implicated in DNA binding, likely through intercalation. To this end, kedarcidin chromophore–induced DNA cleavage is diminished by the addition of divalent cations such as Ca²⁺ and Mg²⁺, which chelatively bind the naphthoic acid group of kedarcidin chromophore and thus lessen its affinity for DNA. Competition experiments with netropsin, a known binder of the DNA minor groove, indicate that kedarcidin likely binds the minor groove as well.
Kedarcidin