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R J Suhadolnik

Publications and source records attributed to R J Suhadolnik.

At least 73 records · Page 4Linked to original sources
PubMed1983

Effect of human fibroblast interferon on the antiviral activity of mammalian cells treated with bleomycin, vincristine, or mitomycin C.

Bleomycin, vincristine, or mitomycin C, when added to HeLa cells simultaneously with human fibroblast interferon (IFN-beta), caused a decrease in cell density and inhibited DNA synthesis compared with HeLa cells treated with IFN-beta alone. However, the IFN-beta-induced antiviral processes were unaffected by the presence of these drugs as determined by in vitro enzyme assays and the development of the antiviral state in the intact HeLa cell. HeLa cells treated with IFN-beta alone or with IFN-beta in combination with bleomycin, vincristine, or mitomycin C were able to induce the double-stranded RNA-dependent adenosine triphosphate:2',5'-oligoadenylic acid adenyltransferase (EC 2.2.2.-) and the double-stranded RNA-dependent protein kinase. Furthermore, the antiviral state as measured by the reduction of plaque-forming units after infection of treated cells (with IFN-beta alone or with IFN-beta plus drugs) with vesicular stomatitis virus was not affected. These results indicate that, under these experimental conditions, the double-stranded RNA-dependent adenosine triphosphate:2',5'-oligoadenylic acid adenyltransferase and protein kinase can be induced by IFN-beta in cells treated with bleomycin, vincristine, or mitomycin C. These cells also develop the antiviral state. These experiments could provide a basis for a careful examination of the effects of interferon on the development of the antiviral state when testing potentially active antineoplastic agents. The possibility that IFN-beta potentiates the cytotoxic effects of bleomycin and mitomycin C on HeLa cells is also discussed.

Antibiotics, Antineoplastic↗
PubMed1983

The life history of poly(ADP-ribose).

We present arguments and data in support of the following sequence of events in ghost cells. Poly(ADP-ribose, ADPR) synthetase, activated by binding to DNA at a break or other anomaly, synthesizes chains of polymer upon itself, adding new residues at the proximal 1" terminus of the growing chain. Free chains of poly(ADPR) are produced by release from the active site or by internal glycohydrolysis of the growing chains without hindering the continued elongation. Subsequent glycohydrolysis cuts the free chains down to monomers. ADP-ribosylation of core histones may involve soluble intermediates of some form. Glycohydrolysis generates a limit digest with only short histone-bound chains. Most ADP-ribosylation of histone H1 occurs by the addition of single free ADPR residues independently of poly(ADPR) synthetase.

Adenosine Diphosphate Ribose↗
PubMed1981

Stereospecificity of the enzymatic dehydrogenation in the biosynthesis of 3-ethylidene-L-azetidine-2-carboxylic acid from isoleucine by Streptomyces cacaoi.

(2RS,3S,4S)-[2-14C,4-3H]Isoleucine and (2S,3S,4R)-[U-14C,4-3H]isoleucine have been prepared by stereospecific syntheses. The addition of these substrates to Streptomyces cacaoi led to the isolation of polyoxins from which 3-ethylidene-L-azetidine-2-carboxylic acid was isolated by hydrolysis. The pro-R hydrogen at C-4 of isoleucine was lost and the pro-S hydrogen was retained in the biosynthesis of 3-ethylidene-L-azetidine-2-carboxylic acid. These results indicate that the enzymatic dehydrogenation of isoleucine to form 3-ethylidene-L-azetidine-2-carboxylic acid involves the antiperiplanar elimination of the hydrogen at C-3 and the pro-R hydrogen at C-4.

Azetidinecarboxylic Acid↗
PubMed1981

Glutamate as the common precursor for the aglycon of the naturally occurring C-nucleoside antibiotics.

Pyrazofurin is one of four naturally occurring C-nucleoside antibiotics; it is elaborated by Streptomyces candidus. The biosynthesis of the pyrazole ring of pyrazofurin has been studied by using 13C- and 14C-labeled acetate. Carbon-13 incorporation into pyrazofurin was observed by proton-decoupled 13C Fourier transform NMR spectroscopy. The incorporation of 14C from [1-14C]acetate was 0.7%. The enrichment of carbons 3, 4, and 5 of pyrazofurin from [2-13C]acetate by S. candidus confirms earlier findings that acetate is converted to glutamate by the combined action of the Krebs cycle and malic enzyme [Elstner, E. F., Suhadolnik, R. J., & Allerhand, A. (1973) J. Biol. Chem. 248, 5385]. Malic enzyme will give rise to [1,2-13C]acetate from [2-13C]acetate. The [1,2-13C]acetate is then converted to glutamate labeled with 13C in carbons 2--5. The 13C incorporation data indicate that carbons 1, 2, 3, and 4, but not 5, of glutamate serve as the four-carbon donor for the carboxamide carbon, C-5, C-4, and C-3, respectively, of the pyrazole ring of pyrazofurin.

Acetates↗
PubMed1981

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.

Adenine Nucleotides↗
PubMed1980

The effect of hemin, adenosine 3',5'-monophosphate and phosphorylated sugars on Met-tRNAfMet deacylase activity in rabbit reticulocyte lysates.

The effect of hemin, phosphorylated sugars, adenosine 3',5'-monophosphate (cyclic AMP) and a number of purines on a specific initiator tRNA deacylase activity in rabbit reticulocytes has been investigated. In the concentration range established to be optimal for maximal stimulation of translation (5.5-30.0 microM), hemin produces a 20-82% inhibition of Met-tRNAfMet deacylation. In contrast, all phosphorylated sugars tested, with the exception of fructose 1,6-diphosphate, are without effect. High concentrations of cyclic AMP (2-4 mM) also significantly inhibit the deacylase activity. The role of hemin and Met-tRNAfMet deacylase in the control of peptide initiation are discussed.

Acyltransferases↗
PubMed1979

Rapid Increase in UDP-Glucose during Early Wheat Embryo Germination.

The cellular content of UDP-glucose in isolated wheat (Triticum aestivum L.) embryo increases 8-fold during the first 40 minutes of imbibition. An additional 3-fold increase in the amount of UDP-glucose was observed in the next 5 hours of germination. This communication also describes a unique, quantitative method to achieve a high sensitivity in a direct determination of UDP-glucose with Na [(32)P]pyrophosphate and UDP-glucose pyrophosphorylase. The sensitivity of the assay for UDP-glucose is 10 picomoles.

Journal Article↗
PubMed1978

Stimulation of the protein synthetic process by adenosine 3':5'-monophosphate and hexose phosphates in gel-filtered rabbit reticulocyte lysates.

The addition of 0.167 to 4.0 mM cAMP to gel-filtered rabbit reticulocyte lysates stimulates the initial rate and the extent of polypeptide synthesis. The stimulation is at the initiation step of polypeptide synthesis as measured by the (i) increased dipeptide, methionyl-valine, accumulation in the presence of the specific initiation inhibitor, pactamycin, and (ii) increased formation of the 40 S and 80 S initiation complex when gel-filtered lysates are incubated with [35S]Met-tRNAFMet. Furthermore, a synergistic stimulation of protein synthesis is observed when cAMP and hexose phosphates (which alone elicit a 1.8-fold stimulation of protein synthesis) are added simultaneously to gel-filtered rabbit reticulocyte lysates. These results indicate that cAMP and hexose phosphates are both essential to maintain the high rate of initiation.

Animals↗