Abstract
2,6-Bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)pyridine (11a) and 1,3-bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene (11b) have been shown to accelerate at 50 mmol·L−1 concentration both the cleavage and mutual isomerization of uridylyl-3′,5′-uridine and uridylyl-2′,5′-uridine by up to two orders of magnitude. The catalytically active ionic forms are the tri- (in the case of 11b) tetra- and pentacations. The pyridine nitrogen is not critical for efficient catalysis, since the activity of 11b is even slightly higher than that of 11a. On the other hand, protonation of the pyridine nitrogen still makes 11a approximately four times more efficient as a catalyst, but only for the cleavage reaction. Interestingly, the respective reactions of adenylyl-3′,5′-adenosine were not accelerated, suggesting that the catalysis is base moiety selective.
Highlights
Artificial ribonucleases, i.e., small molecular compounds that catalyze the cleavage of RNA phosphodiester linkages under neutral conditions, have been the subject of continuous interest since the early 1990s [1,2,3,4]
We report on 2,6-bis(1,4,7,10-tetraazacyclododecan-1-ylmethyl)pyridine (11a) and 1,3-bis(1,4,7, 10-tetraazacyclododecan-1-ylmethyl)benzene (11b) as non-metallic cleaving agents
3′,5′-ApU and 3′,5′-UpA are cleaved much faster than 3′,5′-ApA or other dinucleoside monophosphates that do not contain uracil bases. 3′,5′-UpU is not cleaved, suggesting that both Zn2+(azacrown) moieties are engaged in uracil binding, but the catalytic activity is restored by addition of a third azacrown ligand [31,32,33]
Summary
Artificial ribonucleases, i.e., small molecular compounds that catalyze the cleavage of RNA phosphodiester linkages under neutral conditions, have been the subject of continuous interest since the early 1990s [1,2,3,4]. 2015, 16 dinucleoside-3′,5′-monophosphates at 1.0 mmol·L−1 concentration of the complex at neutral pH and 25 °C [5,6]. Conjugation to an oligonucleotide or peptide nucleic acid (PNA) confers such agents sequence selectivity, turning them into real enzyme mimics [7]. Hybridization between the guiding oligonucleotide and the target sequence increases the local concentration and, activity of the catalytic moiety. This interaction, when sufficiently strong, may render catalysis by the artificial ribonuclease essentially concentration-independent.
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