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Cordycepin analogs of 2-5A: activity in rabbit reticulocyte lysates and extracts from L929 cells

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5019680
; ; ;

Enzymatically and chemically synthesized cordycepin trimer and tetramer analogs of 2-5A (i) inhibit protein synthesis in rabbit reticulocyte lysates (RRL) and intact L929 cells and (ii) bind to and activate partially purified RNase L from RRL to degrade viral mRNA. Direct evidence is presented here that the cordycepin analogs act via activation of RNase L. First, 2-5A and cordycepin tetramer triphosphates (3 x 10/sup -8/ M) degrade mRNA in RRL 55% and 59%, respectively. Second, 2-5A and cordycepin trimer and tetramer triphosphates (5 x 10/sup -9/ M) prevent covalent binding of periodate oxidized p/sub 3/A/sub 4/(/sup 32/P)pC to RNase L from RRL. Third, in incubations of L929 cell extracts, 2-5A and cordycepin trimer and tetramer triphosphates (1 x 10/sup -9/ M) activate RNase L to degrade 18S and 28S rRNA to specific cleavage products. When the same L929 RNase L is bound to 2-5A core cellulose, the RNase L can be activated by 2-5A, but not by cordycepin tetramer triphosphate, to degrade polyU. These data show that the 3'-hydroxyls of 2-5A are not an obligatory requirements for activation of RNase L and subsequent degradation of natural RNAs, but appear to be critical for the enzymatic degradation of a synthetic polyribonucleotide such as polyU.

Research Organization:
Temple Univ. School of Medicine, Philadelphia, PA
OSTI ID:
5019680
Report Number(s):
CONF-8606151-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADENOSINE
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
COVALENCE
DAYS LIVING RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
ERYTHROCYTES
ESTERASES
HYDROLASES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MATERIALS
MESSENGER-RNA
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PHOSPHATES
PHOSPHODIESTERASES
PHOSPHORUS 32
PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PROTEINS
RABBITS
RADIOISOTOPES
REACTION KINETICS
RETICULOCYTES
RIBOSIDES
RNA
RNA-ASE
TRACER TECHNIQUES
VERTEBRATES