Of a series of five newly synthesized 2'-deoxyuridine derivatives, including 5(1-chlorovinyl)-dUrd, (E--(2-bromovinyl)-dUrd, and (E)5-(2-iodovinyl).dUrd, the last two compounds were found to exert a marked inhibitory effect on the replication of herpes simplex virus type 1 [ID50 (mean inhibitory dose), 0.004-0.02 ;tg/mll.Both (E)5(2-bromovinyl).dUrd and (E>5S(2-iodovinyl).dUrd were highly selective in their anti-herpes activity in that they did not affect the growth or metabolism of the host (primary rabbit kidney) cells unless drug concentrations were used that were 5,000-to 10,000-fold greater than those required to inhibit virus multiplication. In this sense (E-5-2-bromovinyl Idoxuridine (5-iodo-2'-deoxyuridine) and trifluorothymidine (5-trifluoromethyl-2'-deoxyuridine) are among the best known antiviral agents currently used in the chemotherapy of-herpesvirus infections (1). Their clinical usefulness is restricted to the topical treatment of local herpes simplex virus (HSV) infections such as herpetic keratitis and "cold sores" (herpes labialis). The unfavorable therapeutic index of Idoxuridine when administered parenterally-as most dramatically exemplified by its inefficacy in patients with herpes simplex encephalitis (2)-has prompted the search for more effective and less toxic anti-herpes agents. In recent years several compounds have been described which are all endowed with selective anti-herpes properties. These compounds include phosphonoacetic acid (3, 4), phosphonoformic acid (5, 6), 9-f3-D-arabinofuranosyladenine (araA) (7, 8), 5-iodo-5'-amino-2',5'-dideoxyuridine (AIDDU) (9, 10), 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) (11, 12), 1-f3-D-arabinofuranosylthymine (araT) (13, 14), 5-iodo-and 5-bromo-2'-deoxycytidine (15, 16), 5,6-dihydro-5-azathymidine (17, 18), and erythro-9-[3-(2-hydroxy- vinyl)-dUrd. These compounds surpassed all previously described anti-herpes agents, including acycloguanosine, in both potency and selectivity, at least in primary rabbit kidney (PRK) cells infected with herpes simplex virus type 1 (HSV-1). Compounds 5-Vinyl-dUrd, 5-ethynyl-dUrd, (E)-5-(2-bromovinyl)-dUrd, and (E)-5-(2-iodovinyl)-dUrd were obtained by condensing the trimethylsilyl derivatives of the appropriate 5-substituted uracils with 2'-deoxy-3,5-di-0-p-toluoyl-a-D-erythropentofuranosyl chloride to give a mixture of the a-and f3-anomers of the protected nucleosides. T anomers were separated by chromatography on silica gel and the p-toluoyl protecting groups were removed by treatment with sodium methoxide in methanol. The results indicated for the biological experiments were all obtained by using the f3-anomers (Fig. 1). The a-anomers were also tested for biological activity, but they were inactive. The synthesis of 25). The synthesis of (E)-5-(2-bromovinyl)-dUrd, (E)-5-(2-iodovinyl)-dUrd, and 5-(1-chlorovinyl)-dUrd has been published elsewhere (ref. 26 and unpublished data). The structures assigned to these compounds were established by elemental analysis and UV and NMR spectroscopy.The sour...

MG-63 cells, a line derived from an osteosarcoma, produced high yields of interferon after superinduction with polyinosinic acid·polycytidylic acid, cycloheximide, and actinomycin D. Advantages of MG-63 cells over diploid fibroblasts as a substrate are: no requirement for aging between confluency and induction, no requirement for priming, and 3.7-fold higher yields per square centimeter of culture surface. Physicochemically and biologically, MG-63 cell interferon resembles fibroblast rather than leukocyte interferon.

Novel infrared‐to‐visible light upconversion devices are demonstrated by fabricating an organic light‐emitting diode with an infrared‐sensitizing layer. With a SnPc:C60 mixed layer as an infrared absorber and fac‐tris(2‐phenylpyridinato) iridium (III) (Irppy3) as an emitter, an infrared‐to‐green up‐conversion device is demonstrated under 830‐nm irradiation (see figure, ITO=indium tin oxide). The maximum photon‐to‐photon conversion efficiency is 2.7% at 15V.

In vitro stimulation of mononuclear cells from human peripheral blood with mitogens causes the release of factors (monokines and lymphokines) which possess distinct biological activities. One such factor, termed 22K, can induce production of human beta-interferon (HuIFN-beta) in cultured human fibroblasts, thereby rendering these cells resistant to virus infection. Here we report the complete purification and partial sequencing (39 N-terminal amino acids) of this factor, whose relative molecular mass was estimated by SDS-polyacrylamide gel electrophoresis to be 17,000 (17K). In addition to an antiviral effect, the pure protein exhibits several other biological activities. Most significantly, intravenous (i.v.) injection of the factor in rabbits caused fever and granulopenia at doses of 0.1-1 microgram per kg, effects which we attribute to a monokine called endogenous pyrogen (EP). In vitro, the protein was scored as positive in a LAF (lymphocyte-activating factor) assay at 0.1-1 ng ml-1. LAF and EP are considered to be members of one family of monokines, called interleukin-1 (IL-1). For this reason, and also because the amino-acid sequence of the 22K factor is at least partially homologous to a complementary DNA-derived IL-1 sequence, we postulate that the 22K factor also belongs to the IL-1 family.