Methyl thiophanate as a DNA minor groove binder produces MT-Cu(II)-DNA ternary complex preferably with AT rich region for initiation of DNA damage.
Interaction of a genotoxic fungicide methyl thiophanate (MT) has been studied in vitro with calf thymus DNA. Fluorescence quenching data revealed the binding constant (K(a)=3.23 x 10(4)M(-1)) and binding capacity (n=1.1) of MT with ctDNA. Ligand displacement studies using specific probes suggested the MT binding at DNA minor groove. The docking analysis further substantiated MT interaction with at least three AT base pairs within the DNA groove. A discernable change in E(0)' value with decreased peak currents in cyclic voltammogram, and peak shifts in CD spectra reflected the formation of MT-ctDNA and MT-ctDNA-Cu(II) complexes. The results elucidate the significance of specific MT-DNA interactions as an initiating event in MT-induced DNA damage.
Saquib
Quaiser
Q
DNA Research Chair, Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Al-Khedhairy
Abdulaziz A
AA
Alarifi
Saud A
SA
Dutta
Sansa
S
Dasgupta
Swagata
S
Musarrat
Javed
J
D000818:Animals; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D005659:Fungicides, Industrial / Q000737:chemistry*; D013875:Thiophanate / Q000737:chemistry*
D005659:Fungicides, Industrial; D013875:Thiophanate; D003300:Copper; D004247:DNA; C427203:calf thymus DNA