867017-50-3Relevant academic research and scientific papers
Opening enediyne scissors wider: pH-dependent DNA photocleavage by meta-diyne lysine conjugates
Kaya, Kemal,Johnson, Madeleine,Alabugin, Igor V.
, p. 748 - 758 (2015/05/13)
Abstract Photochemical activation of meta-diynes incapable of Bergman and C1-C5 cyclizations still leads to efficient double-strand DNA cleavage. Spatial proximity of the two arylethynyl groups is not required for efficient DNA photocleavage by the enediyne-lysine conjugates. Efficiency of the cleavage is a function of the external pH and DNA damage is strongly enhanced at pH 7. The pH-dependence of the DNA photocleavage activity stems from the protonation states of lysine amino groups, the internal electron donors responsible for intramolecular PET quenching and deactivation of the photoreactive excited states. DNA-binding analysis suggests intercalative DNA binding for phenyl substituted conjugate and groove binding for TFP-substituted conjugate. Additional insights in the possible mechanism for DNA damage from the ROS (Reactive Oxygen Species) scavenger experiments found that generation of singlet oxygen is partially involved in the DNA damage. Upon photochemical activation, meta-bis-tetrafluoropyridinylalkyne-lysine conjugates induce pH-dependent DNA ds-photocleavage. Efficiency of DNA damage is strongly enhanced at pH 7. The observed pH-dependence of the DNA photocleavage activity stems from change in the protonation states of lysine amino groups. The ROS (Reactive Oxygen Species) scavenger experiments suggest that singlet oxygen is partially involved in the DNA damage.
DIPEPTIDE ACETYLENE CONJUGATES AND A METHOD FOR PHOTOCLEAVAGE OF DOUBLE STRAND DNA BY DIPEPTIDE ACETYLENE CONJUGATES
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Page/Page column 29-30, (2012/12/13)
Photoreactive DNA cleaving conjugate compounds are provided comprising a DNA cleaving moiety which comprises an aryl alkyne group and a polyfunctional pH-regulated DNA-binding moiety which comprises at least one or two amino groups.
