Kobayashi H, Dorai T, Holland J F, Ohnuma T
Department of Neoplastic Diseases, Mount Sinai School of Medicine, New York, NY 10029.
FEBS Lett. 1993 Mar 15;319(1-2):71-4. doi: 10.1016/0014-5793(93)80039-w.
We designed a hammerhead ribozyme which site-specifically cleaved the GUC sequence in codon 179 of MDR1 mRNA. The cleavage site was 6 amino acids upstream from the drug binding site and was considered sufficiently close to the essential locus for P-glycoprotein function. The ribozyme cleaved the MDR1 mRNA under physiological conditions in vitro. The cleavage was dependent on ribozyme concentration and on incubation time. Mg2+ ion was essential for the cleavage. These results show that a potentially useful tool is at hand which may inactivate MDR1 mRNA and revert the multidrug resistance phenotype.
我们设计了一种锤头状核酶，它能位点特异性地切割多药耐药基因1（MDR1）信使核糖核酸（mRNA）第179密码子中的GUC序列。切割位点位于药物结合位点上游6个氨基酸处，被认为与P-糖蛋白功能的关键位点足够接近。该核酶在体外生理条件下切割MDR1 mRNA。切割依赖于核酶浓度和孵育时间。镁离子对切割至关重要。这些结果表明，一种潜在有用的工具已在手，它可能使MDR1 mRNA失活并逆转多药耐药表型。
