DNA-Destabilizing Agents as an Alternative Approach for Targeting DNA: Mechanisms of Action and Cellular Consequences
Schematic representation of DNA structure. (a) Base pair orientation with x, y, and z axes result in different kind of rotation (tilt, roll, twist) or slipping of the bases (slide, flip) regarding to the helix central axis. (b) Native B-DNA with nearly 11 base pairs within one helix turn. (c) Mono- or bis-intercalation between adjacent base pairs result in an unwinding of the DNA helix (orange arrow on the top) and a lengthening of the DNA helix (Length) depending on the and y Å values that are specific for a defined DNA intercalating compound. (d) Representation of the DNA bending, base flipping, or double strand opening induced by some DNA destabilizing alkylating agents (adduct). Adapted from Calladine and Drew’s schematic boxes representation .
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