Effect of increasing thiolation of the polycytidylic acid strand of poly I:poly C on the alpha, beta and gamma interferon-inducing properties, antiviral and antiproliferative activities.
Double-stranded RNAs induce interferons and cause the development of antiviral and antiproliferative activities. Antiviral activity is related to the production of interferons and other proteins that stimulate various immunologic activities, which appear to contribute to their overall antiproliferative activity. The most active double-stranded RNA, polyI:polyC, was shown to be too toxic for therapeutic use. We conducted selective thiolation of the polyC strand at the five position of the cytosine bases, generating a partially thiolated polyC (MPC) which after annealing with a complimentary unmodified polyI, gave the thiolated double-stranded RNA, pI:MPC. We have explored antiviral and antiproliferative activities at various levels of thiolation and found that optimal responses can be obtained at 7.4% level of thiolation. This compound deserves further study of antiviral and antiproliferative responses in vivo, and eventually clinical exploration. Earlier studies have shown that this and related compounds are active against HIV-1, in human cells, and against DNA polymerases of DNA and RNA tumor viruses.
Chadha
Kailash C
KC
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.
Dembinski
Wlodzimierz E
WE
Dunn
Christopher B
CB
Aradi
Janos
J
Bardos
Thomas J
TJ
Dunn
Joseph A
JA
Ambrus
Julian L
JL
D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects; D011070:Poly I-C / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007369:Interferon Inducers; D013438:Sulfhydryl Compounds; D011070:Poly I-C