1224170-85-7Relevant academic research and scientific papers
Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates
Yang, Wang-Yong,Marrone, Samantha A.,Minors, Nalisha,Zorio, Diego A.R.,Alabugin, Igor V.
, p. 813 - 823 (2011)
Hybrid molecules combining photoactivated aryl acetylenes and a dicationic lysine moiety cause the most efficient double-strand (ds) DNA cleavage known to date for a small molecule. In order to test the connection between the alkylating ability and the DN
Site-specific cleavage of nucleic acids by photoreactive conjugates
-
, (2012/08/28)
A process of forming a double strand cleavage in DNA includes providing a reaction mixture containing double stranded DNA having a break in a first strand defining a target site in a second strand. The method continues by adding to the reaction mixture a
C-lysine conjugates: pH-controlled light-activated reagents for efficient double-stranded DNA cleavage with implications for cancer therapy
Yang, Wang-Yong,Breiner, Boris,Kovalenko, Serguei V.,Ben, Chi,Singh, Mani,LeGrand, Shauna N.,Sang, Qing-Xiang Amy,Strouse, Geoffrey F.,Copland, John A.,Alabugin, Igor V.
, p. 11458 - 11470 (2011/03/17)
Double-stranded DNA cleavage of light-activated lysine conjugates is strongly enhanced at the slightly acidic pH (7) suitable for selective targeting of cancer cells. This enhancement stems from the presence of two amino groups of different basicities. The first amino group plays an auxiliary role by enhancing solubility and affinity to DNA, whereas the second amino group, which is positioned next to the light-activated DNA cleaver, undergoes protonation at the desired pH threshold. This protonation results in two synergetic effects which account for the increased DNA-cleaving ability at the lower pH. First, lysine conjugates show tighter binding to DNA at the lower pH, which is consistent with the anticipated higher degree of interaction between two positively charged ammonium groups with the negatively charged phosphate backbone of DNA. Second, the unproductive pathway which quenches the excited state of the photocleaver through intramolecular electron transfer is eliminated once the donor amino group next to the chromophore is protonated. Experiments in the presence of traps for diffusing radicals show that reactive oxygen species do not contribute significantly to the mechanism of DNA cleavage at the lower pH, which is indicative of tighter binding to DNA under these conditions. This feature is valuable not only because many solid tumors are hypoxic but also because cleavage which does not depend on diffusing species is more localized and efficient. Sequence-selectivity experiments suggest combination of PET and base alkylation as the chemical basis for the observed DNA damage. The utility of these molecules for phototherapy of cancer is confirmed by the drastic increase in toxicity of five conjugates against cancer cell lines upon photoactivation.
