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PMID: 6171822 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Core (2'-5')oligoadenylate and the cordycepin analog: inhibitors of Epstein--Barr virus-induced transformation of human lymphocytes in the absence of interferon.

Doetsch PW, Suhadolnik RJ, Sawada Y, Mosca JD, Flick MB, Reichenbach NL, Dang AQ, Wu JM, Charubala R, Pfleiderer W, Henderson EE

Abstract

The 3'-deoxyadenosine (cordycepin) analog of (2'-5')oligo(A) [(2'-5')oligoadenylate with a triphosphate at the 5' end], synthesized enzymatically from cordycepin 5'-triphosphate in lysed rabbit reticulocytes or L-cell extracts was (i) inhibitory to translation in lysed rabbit reticulocytes and (ii) metabolically stable in extracts of either L cells or C85-5C lymphoblasts. The 5' dephosphorylated (core) (2'-5')oligo(A) and the core cordycepin analog can replace human fibroblast interferon in preventing the transformation of human lymphocytes after infection with Epstein--Barr virus B95-8 (EBV) as determined by the decreased incorporation of [3H]thymidine into cellular DNA and the inhibition of morphological transformation of EBV-infected lymphocytes. Whereas the naturally occurring core (2'-5')oligo(A) was cytotoxic to uninfected lymphocytes and proliferating lymphoblasts, the core cordycepin analog was not. Human leukocyte interferon was more effective than human fibroblast interferon in the inhibition of EBV-induced transformation of human umbilical cord lymphocytes and adult peripheral blood lymphocytes.

MeSH Terms
Adenine Nucleotides/pharmacology Adult Cell Transformation, Viral/drug effects Cells, Cultured Deoxyadenine Nucleotides Drug Stability Female Fetal Blood Herpesvirus 4, Human/genetics Humans Infant, Newborn Interferons/pharmacology Kinetics Lymphocytes/drug effects,metabolism Oligodeoxyribonucleotides/pharmacology Oligonucleotides/pharmacology Oligoribonucleotides/pharmacology Pregnancy
Chemicals
2',5'-oligoadenylate cordycepin analog Adenine Nucleotides Deoxyadenine Nucleotides Oligodeoxyribonucleotides Oligonucleotides Oligoribonucleotides 3'-deoxyadenosine 5'-triphosphate 2',5'-oligoadenylate Interferons
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Doetsch P W
Suhadolnik R J
Sawada Y
Mosca J D
Flick M B
Reichenbach N L
Dang A Q
Wu J M
Charubala R
Pfleiderer W
Henderson E E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1981-11-00
Pages
6699-703
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC349117
Subset
IM
Grants
NCI NIH HHS · CA-12227 · United States
NCI NIH HHS · CA-23999 · United States
NIGMS NIH HHS · GM-26134 · United States
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