Switching between DNA binding modes with a photo- and redox-active DNA-targeting ligand, part II: the influence of the substitution pattern

Abstract

A disulfide-functionalized photoactive DNA ligand is presented that enables the control of its DNA-binding properties by a combination of a photocycloaddition reaction and the redox reactivity of the sulfide/disulfide functionalities....

Photoinduced [2+2] and [4+4] Cycloaddition and Cycloreversion Reactions for the Development of Photocontrollable DNA Binders

“…In a recent study, the photochromic and DNA-binding properties of the benzo [b]quinolizinium ion were further combined with the redox activity of disulfides to generate a dual-mode switch (Scheme 7). [58] As an additional feature, the disulfide group was also used to connect to benzoquinolizinium units such that a more efficient intramolecular cycloaddition reaction is supported. The dialkyl disulfide-linked bisbenzo [b]quinolizinium 14 was shown to bind to DNA in a mixed binding mode of intercalation and groove binding with an affinity of K b = 3.2×10 5 M À 1 (Scheme 7).…”

“…Thus, in analogy to 14 the disulfide 16 binds in a mixed binding mode of intercalation and groove binding with a binding constant of K b = 6.1×10 5 M À 1 . [58] Upon irradiation with λ ex = 365 nm, the disulfide 16 is converted into a mixture of the head-to-head isomers c 16 shh (46 %) and c 16 ahh (54 %) that only interact with DNA by a weak backbone association (Scheme 7). The photocycloaddition of 16 is slower than the one of 14 but still 44 times faster than that of the unsubstituted benzo [b]quinolizinium.…”