RNase Activity of a DNA Minor Groove Binder with a Minimalist Catalytic Motif from RNase A

Towardp-Octiphenyl β-Barrel RNases

“…Although different, often nontrivial experimental conditions and di-or oligomeric substrates and catalysts complicate meaningful interpretations, this activity of β-barrel RNase 1 compared qualitatively well with that reported for other imidazole-rich artificial RNases (see Introduction). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Note that the activity of β-barrel RNase 1 further increases under mildly acidic conditions and in the presence of Zn 2+ (vide infra).…”

“…[1][2][3] Nevertheless, a rich variety of metal-free catalysts have been created over the past two decades, combining many bifunctional alkylamines, imidazoles, guanidinium cations, and mixed dimers with divers recognition motifs. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Intense research on imidazole-rich artificial RNases was stimulated by the fact that pancreatic bovine ribonuclease A (RNase A) acts by general acid/base catalysis using two neighboring histidine residues. 1,[4][5][6] Combination of the intrinsic catalytic activity of imidazole dyads with selective binding has been investigated in conjugates of cyclodextrins, 8 N-phenazinium 9 and acridine 13,14 intercalators, dicationic 1,4-diazabicyclo-[2.2.2]octane 10 and tetracationic spermines, 11 minorgroove selective lexitropsins, 12 and antisense oligonucleotides.…”

“…15,16 In part, high selectivities were reported together with characteristic activities reaching from 10% to 100% RNA cleavage in 4-18 h at temperatures between 37 and 50 °C and catalyst concentrations of 50 µM-2.5 mM. [8][9][10][11][12][13][14][15][16] Results from a different line of research have indicated high importance of β-sheet secondary and perhaps tertiary structures for RNase activity. 7 Barbier and Brack demonstrated that the activity of poly(LK) and, to a smaller extent, that of poly(LR) exceeds that of the "non-β" poly(K), poly(H), poly(AK), poly(PLKLK), "racemized" poly(LK), and monomeric LK-dipeptides (K: L-lysine, R: L-arginine, L: L-leucine, A: L-alanine).…”

“…The design of artificial ribonucleases (RNases) has received much scientific attention because of the medicinal perspective of controlled inhibition of gene expression by selective cleavage of mRNA. − Most artificial RNases with substantial activity known today take advantage of modern bioinorganic chemistry. − Nevertheless, a rich variety of metal-free catalysts have been created over the past two decades, combining many bifunctional alkylamines, imidazoles, guanidinium cations, and mixed dimers with divers recognition motifs. − …”

“…Intense research on imidazole-rich artificial RNases was stimulated by the fact that pancreatic bovine ribonuclease A (RNase A) acts by general acid/base catalysis using two neighboring histidine residues. ,− Combination of the intrinsic catalytic activity of imidazole dyads with selective binding has been investigated in conjugates of cyclodextrins, N -phenazinium 9 and acridine 13,14 intercalators, dicationic 1,4-diazabicyclo[2.2.2]octane 10 and tetracationic spermines, minor-groove selective lexitropsins, and antisense oligonucleotides. , In part, high selectivities were reported together with characteristic activities reaching from 10% to 100% RNA cleavage in 4−18 h at temperatures between 37 and 50 °C and catalyst concentrations of 50 μM−2.5 mM. − …”