1 research outputs found
The <i>N</i><sup>2</sup>‑Furfuryl-deoxyguanosine Adduct Does Not Alter the Structure of B‑DNA
<i>N</i><sup>2</sup>-Furfuryl-deoxyguanosine (fdG) is
carcinogenic DNA adduct that originates from furfuryl alcohol. It
is also a stable structural mimic of the damage induced by the nitrofurazone
family of antibiotics. For the structural and functional studies of
this model <i>N</i><sup>2</sup>-dG adduct, reliable and
rapid access to fdG-modified DNAs are warranted. Toward this end,
here we report the synthesis of fdG-modified DNAs using phosphoramidite
chemistry involving only three steps. The functional integrity of
the modified DNA has been verified by primer extension studies with
DNA polymerases I and IV from <i>E. coli</i>. Introduction
of fdG into a DNA duplex decreases the <i>T</i><sub>m</sub> by ∼1.6 °C/modification. Molecular dynamics simulations
of a DNA duplex bearing the fdG adduct revealed that though the overall
B-DNA structure is maintained, this lesion can disrupt W–C
H-bonding, stacking interactions, and minor groove hydrations to some
extent at the modified site, and these effects lead to slight variations
in the local base pair parameters. Overall, our studies show that
fdG is tolerated at the minor groove of the DNA to a better extent
compared with other bulky DNA damages, and this property will make
it difficult for the DNA repair pathways to detect this adduct