Roelf Datema - Academia.edu (original) (raw)

Papers by Roelf Datema

Research paper thumbnail of Nucleosides and nucleoside analogs as well as pharmaceutical preparations containing these compounds

Research paper thumbnail of Effect of energy depletion on the glycosylation of a viral glycoprotein

Journal of Biological Chemistry

In energy-depleted cells the formation of mannosylphosphoryldolichol is inhibited. Glucosyl-phosp... more In energy-depleted cells the formation of mannosylphosphoryldolichol is inhibited. Glucosyl-phosphoryldolichol, di-N-acetylchitobiosyl-pyrophosphoryl-dolichol and also GDP-mannose are still present, indicating that the formation of mannosyl-phosphoryl-dolichol and hence glycosylation of proteins via the lipid-linked oligosaccharide (Glc)3(Man)9(GlcNAc)2-pyrophosphoryl-dolichol, are under metabolic control. In the energy-depleted cells the endo-beta-N-acetylglucosaminidase H-resistant, lipid-linked oligosaccharides (Man)x(GlcNAc)2-pyrophosphoryl-dolichol (X = 1 to 5) are still formed. Despite the absence of mannosyl-phosphoryl-dolichol protein glycosylation is not blocked. The influenza virus hemagglutinin is glycosylated with endo-beta-N-acetylglucosaminidase H-resistant, but not complex, oligosaccharides. These oligosaccharides can be processed to protein-linked (Man)5(GlcNAc)2 and (Man)4(GlcNAc)2, and may represent glucosylated species. However, the rate at which the hemagglutinin leaves the rough endoplasmic reticulum and, probably therefore, the rate of oligosaccharide-processing are decreased in the energy-depleted cells. Both inhibition of formation of mannosyl-phosphoryl-dolichol and of intracellular migration are reserved when the energy status is brought back to normal levels.

Research paper thumbnail of Metabolism and mode of action of (R)-9-(3,4-dihydroxybutyl)guanine in herpes simplex virus-infected vero cells

Journal of Biological Chemistry

The metabolism and mode of action of the anti-herpes compound buciclovir [R)-9-(3,4-dihydroxybuty... more The metabolism and mode of action of the anti-herpes compound buciclovir [R)-9-(3,4-dihydroxybutyl)-guanine, BCV) has been studied in herpes simplex virus-infected and uninfected Vero cells. In uninfected cells, a low and constant concentration of intracellular BCV was found, while in herpes simplex virus-infected cells, an increasing concentration of BCV phosphates was found due to metabolic trapping. The major phosphorylation product was BCV triphosphate (BCVTP) which was 92% of the total amount of BCV phosphates. BCV phosphates were accumulated to the same extent in cells infected with either a herpes simplex virus type 1 or a herpes simplex virus type 2 strain while thymidine kinase-deficient mutants of herpes simplex virus type 1 were 10 times less efficient in accumulating BCV phosphates. In uninfected Vero cells, the concentration of the phosphorylated forms of BCV was less than 1% of that found in herpes simplex virus-infected cells. The BCVTP formed in herpes simplex virus-infected cells was highly stable, as 80% of the amount of BCVTP was still present even 17 h after removal of extracellular BCV. BCV was a good substrate for herpes simplex virus type 1- and type 2-induced thymidine kinases but not for the cellular cytosol or mitochondrial thymidine kinases. BCV monophosphate could be phosphorylated by cellular guanylate kinase to BCV diphosphate. BCVTP was a selective and competitive inhibitor to deoxyguanosine triphosphate of the purified herpes simplex virus type 1- and type 2-induced DNA polymerases. BCVTP could neither act as an alternative substrate in the herpes simplex virus type 2 or cellular DNA polymerase reactions, nor could [3H]BCV monophosphate be detected in DNA formed by herpes simplex virus type 2 DNA polymerase, or be detected in nucleic acids extracted from herpes simplex virus type 1-infected cells. These data indicate that BCVTP may inhibit the herpes simplex virus-induced DNA polymerase without being incorporated into DNA.

Research paper thumbnail of Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds

Antimicrobial Agents and Chemotherapy

We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice wit... more We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4+ and CD8+ cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo.

Research paper thumbnail of Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry

Antimicrobial Agents and Chemotherapy

SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blockin... more SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blocking virus entry into cells, is an effective inhibitor of virus production and of depletion of human CD4+ T cells in HIV type 1-infected SCID-hu Thy/Liv mice. Steady levels of 100 ng of SID 791 or higher per ml in plasma resulted in statistically significant inhibition of p24 antigen formation. Daily injections of SID 791 caused a dose-dependent decrease in viremia, and this inhibition could be potentiated by coadministration of zidovudine or didanose. The present study suggests that SID 791 alone or in combination with licensed antiviral agents may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. The SCID-hu Thy/Liv model in effect provides a rapid means of assessing the potential of compounds with novel modes of antiviral action, as well as the potential of antiviral drug co...

Research paper thumbnail of Derivatives of purine, process for their preparation and a pharmaceutical preparation

Research paper thumbnail of α nucleoside compounds and a method for treating HBV using said compounds

Research paper thumbnail of Nucleosides and Nucleoside Analogues, Pharmaceutical Composition and Processes for the Preparation of the Compounds

Research paper thumbnail of Use of Nucleosides for the Manufacture of Medicament for Treatment of Diseases Caused by Retrovirus or Hepatitis B Virus

Research paper thumbnail of Nucleosides and nucleotide analogues, pharmaceutical composition and processes for the preparation of the compounds

Research paper thumbnail of Interference with glycosylation of glycoproteins. Inhibition of formation of lipid-linked oligosaccharides in vivo

Biochemical Journal, 1979

Influenza-virus-infected cells were labelled with radioactive sugars and extracted to give fracti... more Influenza-virus-infected cells were labelled with radioactive sugars and extracted to give fractions containing lipid-linked oligosaccharides and glycoproteins. The oligosaccharides linked to lipid were of the ‘high-mannose’ type and contained glucose. In the glycoprotein fraction, radioactivity was associated with virus proteins and found to occur predominantly in the ‘high-mannose’ type of glycopeptides. In the presence of the inhibitors 2-deoxy-D-glucose, 2-deoxy-2-amino-D-glucose (glucosamine), 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose incorporation of radiolabelled sugars into lipid- and protein-linked oligosaccharides was decreased. Kinetic analysis showed that the inhibitors affected first the assembly of lipid-linked oligosaccharides and then protein glycosylation after a lag period. During inhibition by deoxyglucose and the fluoro sugars lipid-linked oligosaccharides were formed that contained oligosaccharides of decreased molecular weight. No such aberrant ...

Research paper thumbnail of The Lipid Pathway of Protein Glycosylation and its Inhibitors: The Biological Significance of Protein-Bound Carbohydrates

Advances in Carbohydrate Chemistry and Biochemistry, 1982

Publisher Summary This chapter focuses on the inhibitors of proteins glycosylation acting at the ... more Publisher Summary This chapter focuses on the inhibitors of proteins glycosylation acting at the level of lipid-linked saccharides formation, compounds that interfere with stages after the transfer of oligosaccharides to the protein. Dolichols are long-chain poly(isoprenol)s found in eukaryotes only and consist of 13–22 isoprene units. The inhibitors of lipid-dependent glycosylation of proteins are also antiviral and antibacterial agents. Glycoproteins are widely distributed in nature, being found in the cytoplasm of cells and in plasma membranes, cell walls, secretions, mucins, and body fluids. Information on the significance of carbohydrate chains of interferon—the protective agent against a number of virus diseases—has been obtained by using the inhibitors of glycosylation during its synthesis. Many aspects of the social behavior of cells are determined by the composition, arrangement, and interaction of cell-surface molecules. Although 2-deoxy- d -arabinose-hexose has been shown mainly to affect glycosylation (in the systems studied so far), its mode of action in more complex, biological systems may not always depend on its well known property.

Research paper thumbnail of Structure-Activity Relationships in Distamycin A Analogues: Effect of Alkyl Groups on the Pyrrole Nitrogen at the Non-amidine End of the Molecule Combined with Methyl Elimination in the Following Ring

Acta Chemica Scandinavica, 1986

Research paper thumbnail of New Virus-Selective Inhibitor of Terminal Glycosylation Increasing Immunological Reactivity of a Viral Glycoprotein

Antiviral Chemistry and Chemotherapy, 1990

Research paper thumbnail of The Chemical Synthesis and Antiviral Properties of an Acyclovir-phospholipid Conjugate

Acta Chemica Scandinavica, 1985

Research paper thumbnail of Inhibition of Glycosylation of Viral Glycoproteins

Biochemical Society Transactions, 1979

Research paper thumbnail of Inhibition of hman immunodeficiency virus type 1 replication by SDZ NIM 811, a non-immunosuppressive cyclosporine analog

Antimicrobial Agents and Chemotherapy

(Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppr... more (Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppressive activity but retains full capacity for binding to cyclophilin and exhibits potent anti-human immunodeficiency virus type 1 (HIV-1) activity. SDZ NIM 811 selectively inhibits HIV-1 replication in T4 lymphocyte cell lines, in a monocytic cell line, and in HeLa T4 cells. Furthermore, its antiviral activity against laboratory strains and against clinical isolates from geographically distinct regions in primary T4 lymphocytes and in primary monocytes (50%o inhibitory concentration = 0.011 to 0.057 ,g/ml) was demonstrated. SDZ NIM 811 does not inhibit proviral gene expression or virus-specific enzyme functions, either free or bound to cyclophilin. The compound does not influence CD4 expression or inhibit fusion between virus-infected and uninfected cells. SDZ NIM 811 was, however, found to block formation of infectious particles from chronically infected cells. Oral administration to mi...

Research paper thumbnail of Didanosine

Antiviral Chemistry and Chemotherapy, 1991

The evaluation and development of didanosine as a therapy for HIV-infection has demonstrated that... more The evaluation and development of didanosine as a therapy for HIV-infection has demonstrated that results of cell-culture studies are only approximate predictors of clinical effects. Whereas the antiviral activity of didanosine is achieved in cell culture at concentrations much higher than those of zidovudine, the two drugs appear to achieve similar effects on markers of HIV-infection at similar clinical doses. The effect of the differing intracellular-half-life of the respective nucleoside triphosphates on the clinical effects is unknown. Similarly, preclinical toxicology studies, while suggesting a low potential for didanosine-induced haematological toxicities, did not predict the findings of peripheral neuropathy and pancreatitis in clinical studies. Thus, the results of controlled clinical studies are required in order to more fully define the therapeutic and safety profile of didanosine.

Research paper thumbnail of The mitochondrial ribosomes of Neurospora crassa II. Comparison of the proteins from Neurospora crassa mitochondrial ribosomes with ribosomal proteins from Neurospora cytoplasm, from rat liver mitochondria and from bacteria

Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1976

1. It has been shown by Datema et al. (Datema, R., Agsteribbe, E. and Kroon, A.M. (1974) Biochim.... more 1. It has been shown by Datema et al. (Datema, R., Agsteribbe, E. and Kroon, A.M. (1974) Biochim. Biophys. Aeta 335, 386-395) that Neurospora mitoehondria isolated in a Mg2÷-containing medium (or after homogenization of the mycelium in th~s medium and subsequent washing of the mitochondrm in EDTA~ontalning medium) possess 80-S ribosomes; mitoehondria homogenized and isolated in EDTA medium yield 73-S ribosomes. The ribosomal proteins of the subun~ of 80-S and 73-S ribosomes were compared by two<lirnensional electrophoresis. The protein patterns of the large, as well as of the small subunits are very similar but not completely identical; the most conspicuous difference is that the large subunit of 80 S contains about eight more proteins than the 10xge subunit of 73 S. * Preceding pape~ in this series is Datema et al. [1]. ** Postal addre~: Bloem~nge110, Groningen0 The Nethe~rl~ds. 228 least 30 proteins in the small subunit. About 50% of these proteins has an isoelectric point below pH 8.6. 6. The pattern of Paracoccus denitrificans is very similar to that of other bacterial ribosomes, the large subunit contains 29, the small subunit 18 proteins.

Research paper thumbnail of The Synthesis and Antiherpetic Activity of DHBG and Some Analogs

Nucleosides and Nucleotides, 1985

Research paper thumbnail of Nucleosides and nucleoside analogs as well as pharmaceutical preparations containing these compounds

Research paper thumbnail of Effect of energy depletion on the glycosylation of a viral glycoprotein

Journal of Biological Chemistry

In energy-depleted cells the formation of mannosylphosphoryldolichol is inhibited. Glucosyl-phosp... more In energy-depleted cells the formation of mannosylphosphoryldolichol is inhibited. Glucosyl-phosphoryldolichol, di-N-acetylchitobiosyl-pyrophosphoryl-dolichol and also GDP-mannose are still present, indicating that the formation of mannosyl-phosphoryl-dolichol and hence glycosylation of proteins via the lipid-linked oligosaccharide (Glc)3(Man)9(GlcNAc)2-pyrophosphoryl-dolichol, are under metabolic control. In the energy-depleted cells the endo-beta-N-acetylglucosaminidase H-resistant, lipid-linked oligosaccharides (Man)x(GlcNAc)2-pyrophosphoryl-dolichol (X = 1 to 5) are still formed. Despite the absence of mannosyl-phosphoryl-dolichol protein glycosylation is not blocked. The influenza virus hemagglutinin is glycosylated with endo-beta-N-acetylglucosaminidase H-resistant, but not complex, oligosaccharides. These oligosaccharides can be processed to protein-linked (Man)5(GlcNAc)2 and (Man)4(GlcNAc)2, and may represent glucosylated species. However, the rate at which the hemagglutinin leaves the rough endoplasmic reticulum and, probably therefore, the rate of oligosaccharide-processing are decreased in the energy-depleted cells. Both inhibition of formation of mannosyl-phosphoryl-dolichol and of intracellular migration are reserved when the energy status is brought back to normal levels.

Research paper thumbnail of Metabolism and mode of action of (R)-9-(3,4-dihydroxybutyl)guanine in herpes simplex virus-infected vero cells

Journal of Biological Chemistry

The metabolism and mode of action of the anti-herpes compound buciclovir [R)-9-(3,4-dihydroxybuty... more The metabolism and mode of action of the anti-herpes compound buciclovir [R)-9-(3,4-dihydroxybutyl)-guanine, BCV) has been studied in herpes simplex virus-infected and uninfected Vero cells. In uninfected cells, a low and constant concentration of intracellular BCV was found, while in herpes simplex virus-infected cells, an increasing concentration of BCV phosphates was found due to metabolic trapping. The major phosphorylation product was BCV triphosphate (BCVTP) which was 92% of the total amount of BCV phosphates. BCV phosphates were accumulated to the same extent in cells infected with either a herpes simplex virus type 1 or a herpes simplex virus type 2 strain while thymidine kinase-deficient mutants of herpes simplex virus type 1 were 10 times less efficient in accumulating BCV phosphates. In uninfected Vero cells, the concentration of the phosphorylated forms of BCV was less than 1% of that found in herpes simplex virus-infected cells. The BCVTP formed in herpes simplex virus-infected cells was highly stable, as 80% of the amount of BCVTP was still present even 17 h after removal of extracellular BCV. BCV was a good substrate for herpes simplex virus type 1- and type 2-induced thymidine kinases but not for the cellular cytosol or mitochondrial thymidine kinases. BCV monophosphate could be phosphorylated by cellular guanylate kinase to BCV diphosphate. BCVTP was a selective and competitive inhibitor to deoxyguanosine triphosphate of the purified herpes simplex virus type 1- and type 2-induced DNA polymerases. BCVTP could neither act as an alternative substrate in the herpes simplex virus type 2 or cellular DNA polymerase reactions, nor could [3H]BCV monophosphate be detected in DNA formed by herpes simplex virus type 2 DNA polymerase, or be detected in nucleic acids extracted from herpes simplex virus type 1-infected cells. These data indicate that BCVTP may inhibit the herpes simplex virus-induced DNA polymerase without being incorporated into DNA.

Research paper thumbnail of Use of standardized SCID-hu Thy/Liv mouse model for preclinical efficacy testing of anti-human immunodeficiency virus type 1 compounds

Antimicrobial Agents and Chemotherapy

We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice wit... more We have developed standardized procedures and practices for infection of SCID-hu Thy/Liv mice with human immunodeficiency virus type 1 for the prophylactic administration of antiviral compounds and for evaluation of the antiviral effect in vivo. Endpoint analyses included quantitation of viral load by intracellular p24 enzyme-linked immunosorbent assay, DNA PCR for the presence of proviral genomes, flow cytometry to measure the representation of CD4+ and CD8+ cells, and cocultivation for the isolation of virus. Efficacy tests in this model are demonstrated with the nucleoside analogs zidovudine and dideoxyinosine and with the nonnucleoside reverse transcriptase inhibitor nevirapine. This small-animal model should be particularly useful in the preclinical prioritization of lead compounds within a common chemical class, in the evaluation of alternative in vivo dosing regimens, and in the determination of appropriate combination therapy in vivo.

Research paper thumbnail of Antiviral efficacy in vivo of the anti-human immunodeficiency virus bicyclam SDZ SID 791 (JM 3100), an inhibitor of infectious cell entry

Antimicrobial Agents and Chemotherapy

SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blockin... more SID 791, a bicyclam inhibiting human immunodeficiency virus (HIV) replication in vitro by blocking virus entry into cells, is an effective inhibitor of virus production and of depletion of human CD4+ T cells in HIV type 1-infected SCID-hu Thy/Liv mice. Steady levels of 100 ng of SID 791 or higher per ml in plasma resulted in statistically significant inhibition of p24 antigen formation. Daily injections of SID 791 caused a dose-dependent decrease in viremia, and this inhibition could be potentiated by coadministration of zidovudine or didanose. The present study suggests that SID 791 alone or in combination with licensed antiviral agents may decrease the virus load in HIV-infected patients and, by extension, that the infectious cell entry step is a valid target for antiviral chemotherapy of HIV disease. The SCID-hu Thy/Liv model in effect provides a rapid means of assessing the potential of compounds with novel modes of antiviral action, as well as the potential of antiviral drug co...

Research paper thumbnail of Derivatives of purine, process for their preparation and a pharmaceutical preparation

Research paper thumbnail of α nucleoside compounds and a method for treating HBV using said compounds

Research paper thumbnail of Nucleosides and Nucleoside Analogues, Pharmaceutical Composition and Processes for the Preparation of the Compounds

Research paper thumbnail of Use of Nucleosides for the Manufacture of Medicament for Treatment of Diseases Caused by Retrovirus or Hepatitis B Virus

Research paper thumbnail of Nucleosides and nucleotide analogues, pharmaceutical composition and processes for the preparation of the compounds

Research paper thumbnail of Interference with glycosylation of glycoproteins. Inhibition of formation of lipid-linked oligosaccharides in vivo

Biochemical Journal, 1979

Influenza-virus-infected cells were labelled with radioactive sugars and extracted to give fracti... more Influenza-virus-infected cells were labelled with radioactive sugars and extracted to give fractions containing lipid-linked oligosaccharides and glycoproteins. The oligosaccharides linked to lipid were of the ‘high-mannose’ type and contained glucose. In the glycoprotein fraction, radioactivity was associated with virus proteins and found to occur predominantly in the ‘high-mannose’ type of glycopeptides. In the presence of the inhibitors 2-deoxy-D-glucose, 2-deoxy-2-amino-D-glucose (glucosamine), 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose incorporation of radiolabelled sugars into lipid- and protein-linked oligosaccharides was decreased. Kinetic analysis showed that the inhibitors affected first the assembly of lipid-linked oligosaccharides and then protein glycosylation after a lag period. During inhibition by deoxyglucose and the fluoro sugars lipid-linked oligosaccharides were formed that contained oligosaccharides of decreased molecular weight. No such aberrant ...

Research paper thumbnail of The Lipid Pathway of Protein Glycosylation and its Inhibitors: The Biological Significance of Protein-Bound Carbohydrates

Advances in Carbohydrate Chemistry and Biochemistry, 1982

Publisher Summary This chapter focuses on the inhibitors of proteins glycosylation acting at the ... more Publisher Summary This chapter focuses on the inhibitors of proteins glycosylation acting at the level of lipid-linked saccharides formation, compounds that interfere with stages after the transfer of oligosaccharides to the protein. Dolichols are long-chain poly(isoprenol)s found in eukaryotes only and consist of 13–22 isoprene units. The inhibitors of lipid-dependent glycosylation of proteins are also antiviral and antibacterial agents. Glycoproteins are widely distributed in nature, being found in the cytoplasm of cells and in plasma membranes, cell walls, secretions, mucins, and body fluids. Information on the significance of carbohydrate chains of interferon—the protective agent against a number of virus diseases—has been obtained by using the inhibitors of glycosylation during its synthesis. Many aspects of the social behavior of cells are determined by the composition, arrangement, and interaction of cell-surface molecules. Although 2-deoxy- d -arabinose-hexose has been shown mainly to affect glycosylation (in the systems studied so far), its mode of action in more complex, biological systems may not always depend on its well known property.

Research paper thumbnail of Structure-Activity Relationships in Distamycin A Analogues: Effect of Alkyl Groups on the Pyrrole Nitrogen at the Non-amidine End of the Molecule Combined with Methyl Elimination in the Following Ring

Acta Chemica Scandinavica, 1986

Research paper thumbnail of New Virus-Selective Inhibitor of Terminal Glycosylation Increasing Immunological Reactivity of a Viral Glycoprotein

Antiviral Chemistry and Chemotherapy, 1990

Research paper thumbnail of The Chemical Synthesis and Antiviral Properties of an Acyclovir-phospholipid Conjugate

Acta Chemica Scandinavica, 1985

Research paper thumbnail of Inhibition of Glycosylation of Viral Glycoproteins

Biochemical Society Transactions, 1979

Research paper thumbnail of Inhibition of hman immunodeficiency virus type 1 replication by SDZ NIM 811, a non-immunosuppressive cyclosporine analog

Antimicrobial Agents and Chemotherapy

(Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppr... more (Me-Ile-4)cyclosporin (SDZ NIM 811) is a 4-substituted cyclosporin which is devoid of immunosuppressive activity but retains full capacity for binding to cyclophilin and exhibits potent anti-human immunodeficiency virus type 1 (HIV-1) activity. SDZ NIM 811 selectively inhibits HIV-1 replication in T4 lymphocyte cell lines, in a monocytic cell line, and in HeLa T4 cells. Furthermore, its antiviral activity against laboratory strains and against clinical isolates from geographically distinct regions in primary T4 lymphocytes and in primary monocytes (50%o inhibitory concentration = 0.011 to 0.057 ,g/ml) was demonstrated. SDZ NIM 811 does not inhibit proviral gene expression or virus-specific enzyme functions, either free or bound to cyclophilin. The compound does not influence CD4 expression or inhibit fusion between virus-infected and uninfected cells. SDZ NIM 811 was, however, found to block formation of infectious particles from chronically infected cells. Oral administration to mi...

Research paper thumbnail of Didanosine

Antiviral Chemistry and Chemotherapy, 1991

The evaluation and development of didanosine as a therapy for HIV-infection has demonstrated that... more The evaluation and development of didanosine as a therapy for HIV-infection has demonstrated that results of cell-culture studies are only approximate predictors of clinical effects. Whereas the antiviral activity of didanosine is achieved in cell culture at concentrations much higher than those of zidovudine, the two drugs appear to achieve similar effects on markers of HIV-infection at similar clinical doses. The effect of the differing intracellular-half-life of the respective nucleoside triphosphates on the clinical effects is unknown. Similarly, preclinical toxicology studies, while suggesting a low potential for didanosine-induced haematological toxicities, did not predict the findings of peripheral neuropathy and pancreatitis in clinical studies. Thus, the results of controlled clinical studies are required in order to more fully define the therapeutic and safety profile of didanosine.

Research paper thumbnail of The mitochondrial ribosomes of Neurospora crassa II. Comparison of the proteins from Neurospora crassa mitochondrial ribosomes with ribosomal proteins from Neurospora cytoplasm, from rat liver mitochondria and from bacteria

Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1976

1. It has been shown by Datema et al. (Datema, R., Agsteribbe, E. and Kroon, A.M. (1974) Biochim.... more 1. It has been shown by Datema et al. (Datema, R., Agsteribbe, E. and Kroon, A.M. (1974) Biochim. Biophys. Aeta 335, 386-395) that Neurospora mitoehondria isolated in a Mg2÷-containing medium (or after homogenization of the mycelium in th~s medium and subsequent washing of the mitochondrm in EDTA~ontalning medium) possess 80-S ribosomes; mitoehondria homogenized and isolated in EDTA medium yield 73-S ribosomes. The ribosomal proteins of the subun~ of 80-S and 73-S ribosomes were compared by two<lirnensional electrophoresis. The protein patterns of the large, as well as of the small subunits are very similar but not completely identical; the most conspicuous difference is that the large subunit of 80 S contains about eight more proteins than the 10xge subunit of 73 S. * Preceding pape~ in this series is Datema et al. [1]. ** Postal addre~: Bloem~nge110, Groningen0 The Nethe~rl~ds. 228 least 30 proteins in the small subunit. About 50% of these proteins has an isoelectric point below pH 8.6. 6. The pattern of Paracoccus denitrificans is very similar to that of other bacterial ribosomes, the large subunit contains 29, the small subunit 18 proteins.

Research paper thumbnail of The Synthesis and Antiherpetic Activity of DHBG and Some Analogs

Nucleosides and Nucleotides, 1985