Netropsin, a minor groove binding ligand: A potential radioprotective agent
Date
2009
Authors
Mishra, K.
Bhardwaj, R.
Chaudhury, N.
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Journal article
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Radiation Research, 2009; 172(6):698-705
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Abstract
Minimizing radiation-induced damages in DNA is an important aspect in the development of chemical radioprotectors. The aim of this study was to evaluate the possible radioprotective ability of the DNA minor groove binding ligand netropsin in an aqueous solution of plasmid DNA (pBR322) and to compare its efficacy with that of Hoechst 33258, a known radioprotector. The radiochemical parameters Dₒ, GSSB and DMF were calculated in pBR322 DNA. Based on a comparison of the DMFs of netropsin and Hoechst 33258, netropsin appeared to be the better radioprotector. The ligand binding site accessibility of the restriction enzyme EcoRI at the ligand-pBR322 complex was assessed using a restriction-digestion assay in irradiated solutions. A distinct ligand-bound site protection in netropsin-DNA was observed in irradiated solutions. However, no site protection was observed in the presence of Hoechst 33258. The possible role of ligand-induced structural stabilization in irradiated aqueous solutions was also investigated using netropsin-calf thymus DNA melting temperature measurements. The greater radioprotective ability of netropsin in solutions of DNA was suggested to be due to its higher binding affinity and its ability to provide higher structural stabilization. EcoRI digestion revealed that hydroxyl radical (OH•) generated by ionizing radiation is not able to radiolyse the netropsin-DNA complex. These results will help in developing better radioprotectors.
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Copyright 2009 Radiation Research Society