Artificial Transcription Factors which Mediate Double‐Strand DNA Cleavage

Abstract

A new family of artificial transcription factor (ATF)-based conjugates have been designed and synthesized as potent chemical nucleases. Polyamides as the important and efficient ATFs were used to modify and activate several anchor compounds. The results demonstrate that the resulting conjugates remarkably promote the rate accelerations and non-random double-strand DNA cleavage activity. Interestingly, the cleavage activity of both the hydrolytic and oxidative agents was promoted efficiently through the modification of the ATFs.

Studies of DNA-Binding and DNA-Cutting Mechanism of an Azamacrocyclic Cerium Complex with Carboxyl Branch

“…However, the linear DNA was not observed under present experimental conditions. This situation accords with random single-strand breaks and indicates the participation of a single-strand cleavage mechanism [25], which is very similar to that reported [26] using the Cu(II) complex with triazacyclononane cleaving agent.…”

Progress in artificial metallonucleases

“…A higher activity and an interesting double strand cleavage propensity were subsequently reported with a related conjugate bearing a bis-cyclen-Zn(II) 2 complex. 79 The second type of conjugate is obtained by coupling metal complexes and DNA or RNA nucleobases. An example is the uracil-Zn(II)-cyclen conjugate reported by Lin, Yu and co-workers (Fig.…”

“…Other two problems that have been scarcely addressed are double strand cleavage and sequence selectivity, which are essential for application of hydrolytic agents as artificial restriction enzymes. Double strand cleavage has been observed quite rarely, notably with minor groove binder conjugates featuring two metal chelating moieties 79 or with multivalent nanoparticles 54 and few others. In both such examples the double strand cleavage is a consequence of the presence of two or more catalytic units on the hydrolytic agent, which likely operate simultaneously on the two strands.…”

Insight into DNA Minor Groove Unspecific Binding of Pyrrole Polyamide

“…Circular dichroism spectropolarimetry was a powerful tool to detect and characterize DNA secondary structures changes with interaction of binding molecules. , Positive ellipticity at 300–360 nm as typical minor groove binding signals induced by polyamides has been widely reported. − Our previous work focused on the modification of less reactive DNA cleavage molecules by Py-Im polyamide, aimed at the enhancement of the double-strand cleavage selectivity. − Recently, we synthesized an eight pyrrole-containing polyamide appended with cyclen moiety ( Py 4 - γ -Py 4 - γ -cyclen , Scheme ), and expected to improve specific DNA cleavage ablility in the presence of metal ions. Interestingly, titration experiments of the polyamide into a solution of ct-DNA presented a group of unusual CD induced signals, which differed from a well-known increasing positive absorption around 335 nm.…”

“…Positive ellipticity at 300-360 nm as a typical minor groove binding signals induced by polyamides have been widely reported [17][18][19] . Our previous work focused on the modification of less reactive DNA cleavage molecules by Py-Im polyamide, aimed at the enhancement of the double-strand cleavage selectivity [20][21][22] . Recently, we synthesized an eight pyrrole-containing polyamide appended with cyclen moiety (Py 4 -γ-Py 4 -γ-cyclen, Scheme 1), and expected to improve specific DNA cleavage ablility in the presence of metal ions.…”