Interaction of N-trifluoroacetyladriamycin-14-O-hemiadipate with chicken leukemia RNA polymerase. Formation of drug-enzyme complex.

Abstract

The biochemical mechanism of the N-trifluoroacetyladriamycin-14-O-hemiadipate-induced inhibition of RNA synthesis in vitro by chicken (myeloblastosis) leukemia RNA polymerase II was studied. The inhibition was found to be dependent upon preincubation of the drug with the enzyme prior to enzyme assays, suggesting that drug-enzyme interactions occur. A drug-enzyme association complex was subsequently isolated through glycerol gradient sedimentation and further characterized by fluorescent microscopic studies. The drug was dissociated from the complex upon sodium dodecyl sulfate (SDS)-gel electrophoresis, revealing the non-covalent nature of the binding between the drug and the RNA polymerase.

• Authors: R Y Chuang, L F Chuang, M Israel
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 35 Issue 8 Pg. 1293-7 (Apr 15 1986) ISSN: 0006-2952 [Print] England
• PMID: 3754449 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Neoplasm
• Doxorubicin
• N-trifluoroacetyladriamycin-14-O-hemiadipate
• RNA Polymerase II

Topics

• Animals
• Avian Leukosis (enzymology)
• Chickens
• Doxorubicin (analogs & derivatives, metabolism, pharmacology)
• Electrophoresis, Polyacrylamide Gel
• Microscopy, Fluorescence
• RNA Polymerase II (antagonists & inhibitors, metabolism)
• RNA, Neoplasm (biosynthesis)
• Time Factors