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Nuclease resistant hammerhead motif: from '5-ribo' to '3-ribo' model

J Matulic-Adamic¹, A T Daniher, C Gonzalez

¹Department of Chemistry & Biochemistry, Ribozyme Pharmaceuticals, Inc., Boulder, CO 80301, USA.

Bioorganic & Medicinal Chemistry Letters

|February 18, 1999

Abstract:

Previously developed '5-ribo' nuclease stabilized hammerhead motif was further refined by systematic incorporation of 1-(beta-D-xylofuranosyl) adenine (xA) and 1-(beta-D-xylofuranosyl) guanine (xG) in the place of conserved ribopurine residues of the catalytic core. Modified ribozymes substituted with xA at positions A15.1 and A6 demonstrated catalytic activity close to the parent stabilized ribozyme. Analogous guanosine substitutions at positions G5, G8, and G12 substantially lowered catalytic rates.

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