Conjugates of a Dinuclear Zinc(II) Complex and DNA Oligomers as Novel Sequence-Selective Artificial Ribonucleases

Abstract

The sequence-selective scission of RNA has been attracting interest because of its potential applications, both in vivo and in vitro. [1] Artificial ribonucleases have been prepared by attaching catalytically active metal ions (mostly lanthanide ions) to DNA oligomers as sequence-recognizing moieties. [2±4] However, the following limitations remain: 1) divalent metal ions such as Zn II and Mg II , which are widely spread in vivo, [5] cannot be used, and 2) selective scission can be achieved only when free metal ions are absent in the reaction mixtures (otherwise, nonselective scission becomes dominant). Further progress is desirable.It has previously been shown that dinuclear Zn II complexes hydrolyze RNA under physiological conditions. [6,7] Although the Zn II ion itself is a rather poor candidate for RNA hydrolysis, a notable activity appears when two of them cooperate. Here we report that conjugates of a dinuclear Zn II complex and DNA oligomers selectively hydrolyze RNA at the target site, even in the presence of a considerable amount of free Zn II ions.Phosphoramidite monomer 1 containing a N,N,N',N'-tetrakis(2-pyridylmethyl)-3,5-bis(aminomethyl)benzene (TPBA) group was prepared according to Scheme 1. By use of 1 and CH 2 OH

Zinc(II) tweezers containing artificial peptides mimicking the active site of phosphotriesterase: The catalyzed hydrolysis of the toxic organophosphate parathion

“…Recently, in order to increase the reactivity of artificial hydrolytic catalysts, several hydrolytic metalloenzyme models containing diand trinuclear zinc(II) complexes have been designed and studied to account for or mimic the function played by the cooperativity of two or three zinc(II) ions, as occurs in several phosphatases and nucleases [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. In these systems, we found that the multinuclear complexes were generally more active than their corresponding mononuclear ones.…”

Fluorophore-linked zinc(II)dipicolylamine coordination complexes as sensors for phosphatidylserine-containing membranes

“…In other words, rationally designed coordination complexes may be useful as mimics of annexin V. Several phosphate chemosensors with Zn 2C -coordinated binding sites have been described in the literature. [17][18][19] For example, Hamachi and co-workers recently described an anthracene-based sensor with two zinc dipicolylamine (Zn 2C -DPA) units (Fig. 2).…”

“…4). The design retains the Zn 2C -DPA affinity units, attached in a meta orientation to a phenyl ring, 18 which is in turn linked to a 7-nitrobenz-2-oxa-1,3-diaza-4-yl (NBD) fluorophore. The NBD fluorophore is excited at 470 nm and exhibits a broad emission centered at 530 nm, which limits its use in microscopy and flow cytometry applications; nevertheless, its environmental sensitivity makes it useful for the mechanistic experiments performed here.…”

A novel 1,2,4-triazole-based copper(II) complex: Synthesis, characterization, magnetic property and nuclease activity

“…A variety of metal complexes which can promote the hydrolysis of DNA and phosphodiesters have been reported [10][11][12][13][14][15][16][17][18][19]. Among several types of transition metal complexes used as hydrolytic cleavage agents, copper(II) complexes have attracted special attention, which has been observed as cofactor in many nucleases [20,21].…”