Core (2'-5')oligoadenylate and the cordycepin analog: inhibitors of Epstein--Barr virus-induced transformation of human lymphocytes in the absence of interferon.
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.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000328:Adult; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D003838:Deoxyadenine Nucleotides; D004355:Drug Stability; D005260:Female; D005312:Fetal Blood; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007372:Interferons / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D009841:Oligonucleotides / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000494:pharmacology*; D011247:Pregnancy
C032558:2',5'-oligoadenylate cordycepin analog; D000227:Adenine Nucleotides; D003838:Deoxyadenine Nucleotides; D009838:Oligodeoxyribonucleotides; D009841:Oligonucleotides; D009843:Oligoribonucleotides; C011746:3'-deoxyadenosine 5'-triphosphate; C023505:2',5'-oligoadenylate; D007372:Interferons