Suppression of smooth muscle cell proliferation by a c-myc RNA-cleaving deoxyribozyme
| Autor: | Andrew King, Lun-Quan Sun, Murray J. Cairns, Craig Witherington, Li Wang, Wayne Gerlach |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cell
Deoxyribozyme DNA Recombinant DNA Single-Stranded Transfection Biochemistry Muscle Smooth Vascular Proto-Oncogene Proteins c-myc chemistry.chemical_compound Gene expression medicine Animals RNA Messenger Molecular Biology Nuclease biology Cell growth RNA Cell Biology DNA Catalytic Cell biology Rats medicine.anatomical_structure chemistry Drug Design Protein Biosynthesis biology.protein DNA Cell Division |
| Zdroj: | The Journal of biological chemistry. 274(24) |
| ISSN: | 0021-9258 4262-4266 |
| Popis: | A small catalytic DNA molecule targeting c-myc RNA was found to be a potent inhibitor of smooth muscle cell (SMC) proliferation. The catalytic domain of this molecule was based on that previously derived by in vitro selection (Santoro, S. W., and Joyce, G. F. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 4262-4266) and is known as the "10-23" general purpose RNA-cleaving deoxyribozyme. In addition to inhibiting SMC proliferation at low concentration, this molecule (targeting the translation initiation region of c-myc RNA) was found to efficiently cleave its full-length substrate in vitro and down-regulate c-myc gene expression in smooth muscle cells. The serum nuclease stability of this molecule was enhanced without substantial loss of kinetic efficiency by inclusion of a 3'-3'-internucleotide inversion at the 3'-terminal. The extent of SMC suppression was found to be influenced by the length of the substrate binding arms. This correlated to some extent with catalytic activity in both the short substrate under multiple turnover conditions and the full-length substrate under single turnover conditions, with the 9 + 9 base arm molecule producing the greatest activity. |
| Databáze: | OpenAIRE |
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