Abstract
Four base-modified hammerhead ribozyme/substrate complexes were constructed in which single guanosine (1) residues were replaced by 3-deazaguanosine (2) in the positions G5, G8, GL2.1, and G12. The base-modified ribozyme complexes were prepared by solid-phase synthesis of oligoribonucleotides employing the novel phosphoramidite 3 derived from 2. Phosphoramidite 3 carried a phenoxyacetyl group at the amino function and a diphenylcarbamoyl residue at the oxo group of the nucleobase. The 2′-hydroxy group was blocked with a triisopropylsilyl residue. Kinetic analysis of the phosphodiester hydrolysis showed a moderate decrease of the ribozyme catalytic activity when the residues G5 or G8 were replaced by 3-deazaguanosine and a 200-fold decrease when G12 was substituted. A 6-fold catalytic increase occurred when 3-deazaguanosine was replacing GL2.1 in the loop region. The data indicate that the N(3) atom of compound 2, in particular at position G12 is critical for the ribozyme activity.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.