Structure-function correlations derived from faster variants of a RNA ligase deoxyribozyme
We previously reported the in vitro selection of several Mg²⁺‐dependent deoxyribozymes (DNA enzymes) that synthesize a 2′–5′ RNA linkage from a 2′,3′‐cyclic phosphate and a 5′‐hydroxyl. Here we subjected the 9A2 deoxyribozyme to re‐selection for improved ligation rate. We found two new DNA enzymes (7Z81 and 7Z48) that contain the catalytic core of 7Q10, a previously reported small deoxyribozyme that is unrelated in sequence to 9A2. A third new DNA enzyme (7Z101) is unrelated to either 7Q10 or 9A2. The new 7Z81 and 7Z48 DNA enzymes have ligation rates over an order of magnitude higher than that of 7Q10 itself and they have additional sequence elements that correlate with these faster rates. Our findings provide insight into structure–function relationships of catalytic nucleic acids.
Additional Information© 2004 Oxford University Press. Received November 17, 2003; Revised and Accepted January 13, 2004. This research was supported by the Burroughs Wellcome Fund (New Investigator Award in the Basic Pharmacological Sciences), the March of Dimes Birth Defects Foundation (Research Grant no. 5‐FY02‐271), the National Institutes of Health (GM‐65966), the American Chemical Society Petroleum Research Fund (38803‐G4) and the UIUC Department of Chemistry (all to S.K.S.). S.K.S. is the recipient of a fellowship from The David and Lucile Packard Foundation.
Published - gkh263.pdf