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Table 2 Cleavage Rate constants for cleavage of S-30 by Chemically Modified Mrz-12/12.

From: Redesigned and chemically-modified hammerhead ribozymes with improved activity and serum stability

Miniribozyme (Mrz-12/12) C3 U4 U7 C15.2 3' end Cleavage rate constant (min-1) Relative Stability
A - - - - - 4.2 ± 0.3 1
B F NH2 NH2 F - 0.30 ± 0.05 -
C - NH2 NH2 - - 0.18 ± 0.01 -
D - NH2 - - - 0.30 ± 0.03 -
E - - NH2 - - 7.7 ± 0.8 -
F - dT - - - 0.014 ± 0.005 -
G - dU - - - 0.024 ± 0.007 -
H - OMe - - - 0.01 ± 0.007 -
I - ps - - - 3.9 ± 0.06 -
J OMe ps OMe OMe psps 7.3 ± 0.7 1400
K OMe NH2 OMe OMe - 0.6 ± 0.1 8600
Rz-12/12-L - NH2 - - - 0.05 ± 0.009 -
  1. Cleavage conditions; 37°C, pH 7.6, 10 mM MgCl2. [Rz] = 1 μM, [S30] = 5 nM. (- = unmodified, ie 2'OH). F = 2'-fluoro, NH2 = 2'-amino, dT = 2'-deoxythymidine, dU = 2'-deoxyuridine, OMe = 2'-O-methyl, ps = 3' phosphorothioate linkage. Stability is defined as the time required in 10% human serum to degrade 75% of full-length ribozyme, relative to unmodified miniribozyme A.
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BMC Chemical Biology

ISSN: 1472-6769