Catalytic activity and stability of hammerhead ribozymes containing 2'-acetamido-2'-deoxyribonucleosides.

Abstract:

:Hammerhead ribozymes may be of great therapeutic importance, since they can, in theory, be developed to cleave any undesired target RNA. In order to design ribozymes which are stable against endogenous RNases, we incorporated 2'-acetamido-2'-deoxynucleosides in the catalytic core of a hammerhead ribozyme. The 2'-acetamido function has, like the hydroxyl group, both proton donor and proton acceptor capacities, which seem to be crucial for efficient catalytic activity. However, the presence of 2'-acetamido-2'-deoxypyrimidine residues in the catalytic core caused a considerable drop in cleavage rate. Replacement of the purine residues led to complete loss of the catalytic activity. Surprisingly, these 2'-modifications showed no beneficial influence on the stability of the ribozymes against RNases present in cell culture supernatant containing 10% fetal calf serum.

authors

Hendrix C,Mahieu M,Anné J,Van Calenbergh S,Van Aerschot A,Content J,Herdewijn P

doi

10.1006/bbrc.1995.1628

subject

Has Abstract

pub_date

1995-05-05 00:00:00

pages

67-73

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006291X85716282

journal_volume

210

pub_type

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