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PubMed2004

Challenges in antimicrobial drug discovery and the potential of nucleoside antibiotics.

Antimicrobial resistance in hospital and community settings is growing at an alarming rate and has been attributed to such organisms as methicillin-resistant staphylococcus aureus, staphylococci with decreased susceptibility to vancomycin, vancomycin-resistant enterococci, multi-drug resistant pseudomonas spp., klebsiella spp., enterobacter spp, and acinetobacter spp., as well as Streptococcus pneumoniae with decreased susceptibility to penicillin and other antibacterials. To address the need for new therapies to combat resistant organisms, drug companies are refocusing their discovery efforts on developing novel agents with new mechanisms of action. The hope is that rapidly emerging technologies including combinatorial chemistry, high throughput screening, proteomics and microbial genomics will have a positive impact on antimicrobial drug discovery. These technologies should aid in the identification of novel drug targets and compounds with unique mechanisms of action other than those currently provided by the traditional antibiotics. Nucleosides are one class of compounds worthy of further investigation as antibacterials since some derivatives have shown moderate to good activity against specific bacterial strains. For example, 5'-peptidyl nucleoside derivatives can inhibit peptide deformylase, an enzyme essential for bacterial survival that is not vital to human cells. This review also includes a list of miscellaneous nucleosides that have been synthesized as potential antibacterials. More detailed investigations on structure, as it relates to the antimicrobial activity of the various classes of nucleosides, need to be conducted in order to maximize the potential of developing a potent nucleoside for the treatment of bacterial infections. This review begins with an introduction to terms followed by discussions regarding the general background and relevance for developing novel antimicrobial agents. Challenges facing the antimicrobial drug discovery process are discussed along with relevant drug targets. An overview of nucleoside chemistry as it relates to antimicrobial activity is presented, followed by a discussion of the evidence which supports the potential of this class of compounds to yield the novel antimicrobial therapies needed in the new millennium.

Animals↗
PubMed2005

Lipid nucleoside conjugates for the treatment of cancer.

Phospholipid nucleoside conjugates and nucleosides with chemical additions to the hydroxyl and amino moieties have been used since the 1970s in order to increase the biological activity of the parent compound. Previous investigators have found that adding lipid moieties to ara-C or chemically linking ara-C to a phospholipid creates a prodrug that exhibits superior cytotoxic activity compared to ara-C alone when used in animal tumor models. The novel ara-C molecules reveal different pharmacological profiles from the parent compound such as decreased catabolism by cytidine deaminase, increased plasma half-life, and release of nucleoside monophosphate, a reaction that bypasses the rate limiting initial nucleoside phosphorylation. Additionally, these compounds were able to penetrate the blood-brain barrier and were active against tumor cells implanted i.c. The purpose of this review is to briefly cover the history and successes of previous investigators who have synthesized and tested these phospholipid ara-C conjugates, to discuss recent phospholipid ara-C and fludarabine conjugates, and to discuss the synthetic design and synthesis of a novel phospholipid gemcitabine conjugate. These phospholipid nucleoside conjugates possess the potential to have superior anti-neoplastic cytotoxicity profiles with fewer side effects than the parent nucleoside and merit further investigation.

Animals↗
PubMed2002

L-nucleosides: antiviral activity and molecular mechanism.

Drug discovery for antiviral chemotherapy has provided the effective treatment of numerous viral diseases. Among antiviral agents used in therapy, nucleoside analogues have been particularly useful. In fact, almost twenty nucleosides are currently used in antiviral therapy, seven of which are for the treatment of HIV infection. In the search for new and effective agents within this class, the focus has recently expanded on L-analogues, characterized by opposite configuration compared to the natural D-nucleosides. The interest in L-nucleosides has risen since the discovery of 3TC, one of the most important drugs used in the treatment of AIDS and hepatitis B infection. This review will discuss the latest advances in L-nucleosides as antiviral agents with a particular focus on the synthesis and molecular mechanism as well as metabolic differences between L- and D-nucleosides.

Animals↗
PubMed2005

Olefin metathesis route to antiviral nucleosides.

The success of the early nucleoside agents, the toxicity and metabolic instability of many nucleoside analogues and the effects of viral pathogens on public health are driving the design, synthesis and evaluation of new nucleoside analogues. In this context, a powerful reaction has emerged over the past decade that has fundamentally changed the outlook on nucleoside chemistry: the olefin metathesis reaction. This review is designed to give an overview of the synthesis of some nucleosides of biological interest, according to their structural types (e.g., neplanocins and aristeromycin analogues, 2',3'-unsaturated nucleoside analogues, and acyclonucleosides), using metathesis reactions by employing either the alkoxy imido molybdenum catalyst developed by Schrock and various ruthenium carbene catalysts developed by Grubbs, Hoveyda-Grubbs and Nolan.

Alkenes↗
PubMed2006

Nucleoside analog inhibitors of hepatitis C virus replication.

Of the 30 compounds currently marketed in the United States for treatment of viral infections, 15 are nucleoside analogs, demonstrating the utility of this class of compound as a source of antiviral drugs. The success of nucleoside analogs in treating other viral infections provides a compelling rationale for the significant effort that is currently being devoted to the discovery and development of nucleoside analogs to treat infection by hepatitis C virus (HCV) that may lead to improvements in response rates compared to currently available therapies. Several different approaches have been adopted to identify promising analogs, including the use of surrogate viruses in cell culture assays, screening in the cell-based bicistronic HCV replicon assay, and screening nucleoside triphosphates for the ability to inhibit the activity of the HCV RNA-dependent RNA polymerase in vitro. Several classes of ribonucleoside analogs with modifications of the ribose inhibit HCV replication. Nucleoside analogs incorporating a 2'-C-methyl modification are potent inhibitors in the replicon assay in the absence of cytotoxicity, and appear to exert their inhibition by acting as functional chain terminators of RNA synthesis. NM283, a prodrug of 2'-C-methylcytidine, has entered clinical trials and demonstrated viral load reductions in subjects infected with genotype 1 HCV, a genotype known to be difficult to treat effectively with currently approved therapies. Overall, results to date offer encouragement that improved therapies to treat HCV infection including newly developed nucleoside analogs may become available within the next few years.

Animals↗
PubMed2005

Urinary nucleosides as biological markers for patients with colorectal cancer.

AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer. METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10 patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method. RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%). Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke's stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32) and 91% (10/11) in response group and progressive group, respectively. CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer.

Adult↗
PubMed2005

Apoptosis induced by nucleosides in the human hepatoma HepG2.

AIM: To investigate the apoptotic effects of nucleosides on the human hepatoma HepG2. METHODS: The nucleosides included inosine (I), cytidine (C), uridine (U), thymidine (T), adenosine (A), and guanosine (G). Cells were incubated by the mediums with or without nucleosides at 37 degree C in a 50 mL/L CO(2) humidified atmosphere. RESULTS: It was found that the cell viabilities were significantly decreased, when cells were treated with 30 mmol/L I, 30 mmol/L C, 30 mmol/L U, 30 mmol/L T, 0.5 mmol/L A, and 0.5 mmol/L G after 12 h incubation (P< 0.05). About the apoptotic phenomenon, the cell percentages of sub-G(1) cells were significantly increased in the mediums containing nucleosides such as C, U, T, A, and G (P< 0.05). Furthermore, the caspase-3 activity was increased, when the cells were incubated with T (P< 0.05). The protein expressions of p53 and p21 showed no difference in each group. To investigate the mechanism of apoptosis induced by nucleosides, it was found that the contents of soluble Fas ligand contents were increased in HepG2 cells following I, U, T, and A treatment (P< 0.05). But, TNF-alpha and cytochrome c were undetectable. CONCLUSION: Thymidine may induce the apoptosis in HepG2, but the effective dosages and reactive time must be investigated in the future study. However, the apoptosis-inducing abilities of other nucleosides were still unclear in this study.

Apoptosis↗
PubMed1992

Mammalian nitrobenzylthioinosine-sensitive nucleoside transport proteins. Immunological evidence that transporters differing in size and inhibitor specificity share sequence homology.

Polyclonal antibodies were raised against the nitrobenzylthioinosine (NBMPR)-sensitive nucleoside transporter of human erythrocyte membranes. On Western blots of these membranes they labeled the broad "band 4.5" region (average apparent M(r) 55,000), which contains both the nucleoside and glucose transport proteins. However, they did not recognize the glucose transporter when this was prepared free of nucleoside transporter by expression from a cDNA clone. Their specificity for the nucleoside transporter was confirmed by the ability to immunoadsorb NBMPR- but not cytochalasin B-binding sites from a detergent-solubilized mixture of band 4.5 proteins. Although a large proportion of the antibodies recognized extracellular epitopes, these appeared to be located primarily on the polypeptide moiety of the glycoprotein, as demonstrated by the ability of the antibodies strongly to label the deglycosylated transporter (apparent M(r) 45,000) on Western blots. The antibodies were species-cross-reactive, recognizing nucleoside transporters from pig and rabbit erythrocytes and from rat liver. The pig protein is similar to the human transporter in its inhibitor sensitivity but is considerably larger (apparent M(r) 57,000 after deglycosylation). In contrast, the rat protein is similar in size to the human transporter (apparent M(r) 45,000 after deglycosylation) but much less sensitive to the inhibitors dilazep and dipyridamole. These findings indicate that despite their differences in size and inhibitor specificity, the NBMPR-sensitive nucleoside transporters of these mammalian species are related in amino acid sequence.

Affinity Labels↗
PubMed2004

[Simultaneous determination of ergosterol, nucleosides and their bases from natural and cultured Cordyceps by pressurized solvent extraction and high performance liquid chromatography].

AIM: To establish a simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps by HPLC coupled with pressurized solvent extraction (PSE). METHODS: The extraction was performed by using PSE and the PSE condition was optimized by using orthogonal test, the contents of ergosterol, nucleosides and their bases in Cordyceps were determined by HPLC. RESULTS: The optimized condition of PSE extraction for ergosterol, nucleosides and their bases in Cordyceps was obtained as follow: solvent, methanol; temperature, 160 degrees C; static extraction time, 5 min; pressure, 10 MPa and one extraction cycle and one time. A ZORBAX NH2 column (250 mm x 4.6 mm ID, 5 microm) and a ZORBAX NH2 guard column (12.5 mm x 4.6 mm ID, 5 microm) were used for simultaneous determination of ergosterol, nucleosides and their bases. Solvents that constituted the mobile phase were A (acetonitrile) and B (10 mmol x L(-1) ammonium acetate in water). The elution conditions applied were: 0 -5.0 min, linear gradient 0 --> 15% B; 5.0-25.0 min, linear gradient 15% --> 20% B; 25.0 - 35.0 min, linear gradient 20% --> 40% B; 35.0 - 45.0 min, linear gradient 40% --> 80% B; 45.0 -50.0 min, 80% B isocratic. The flow-rate was 0. 6 mL x min(-1) and the injection volume was 20 microL. The system operated at 25 degrees C. Ergosterol was monitored and quantified at 275 nm, nucleosides and their bases at 254 nm. CONCLUSION: High performance liquid chromatography coupled with pressurized solvent extraction is a rapid and simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps.

Adenosine↗
PubMed1990

Nucleoside diphosphate kinase from Myxococcus xanthus. II. Biochemical characterization.

The gene that encodes the 16-kDa GTP-binding protein from Myxococcus xanthus has been cloned, and its DNA sequence has been determined. The gene has been expressed in Escherichia coli by using the lacZ promoter, and its gene product was overproduced (Muñoz-Dorado, J., Inouye, M., and Inouye, S. (1990) J. Biol. Chem. 265, 2702-2706). The gene product thus overproduced in E. coli was purified to homogeneity by a simple four-step procedure and crystallized. Gel filtration of the purified protein revealed that the protein forms a complex of an apparent molecular weight of 50,000, indicating that it exists as a trimer in the cell. It was found that the purified protein can bind not only GTP, but also equally well the other nucleoside diphosphates and triphosphates with no specificity for either the base or the sugar. Nucleoside monophosphates, Pi, and pyrophosphate do not bind to the protein. In the presence of Mg2+, the protein hydrolyzes nucleoside triphosphates to diphosphates and Pi. However, in the presence of EDTA, most of the phosphate remains bound to the protein. The phosphorylated protein can then transfer the phosphate group to a nucleoside diphosphate to form the corresponding nucleoside triphosphate in the presence of Mg2+. The reaction is reversible, and it is considered to occur by a two-step ping-pong mechanism. These results unambiguously demonstrate that the M. xanthus 16-kDa GTP-binding protein is a nucleoside diphosphate kinase.

Adenosine Triphosphate↗
PubMed1989

Classification of lung cancer patients and controls by chromatography of modified nucleosides in serum.

A wide spectrum of modified nucleosides has been quantified by high-performance liquid chromatography in serum of 49 male lung cancer patients, 35 patients with other cancers, and 48 patients hospitalized for nonneoplastic diseases. Data for 29 modified nucleoside peaks were normalized to an internal standard and analyzed by discriminant analysis and stepwise discriminant analysis. A model based on peaks selected by a stepwise discriminant procedure correctly classified 79% of the cancer and 75% of the noncancer subjects. It also demonstrated 84% sensitivity and 79% specificity when comparing lung cancer to noncancer subjects, and 80% sensitivity and 55% specificity in comparing lung cancer to other cancers. The nucleoside peaks having the greatest influence on the models varied dependent on the subgroups compared, confirming the importance of quantifying a wide array of nucleosides. These data support and expand previous studies which reported the utility of measuring modified nucleoside levels in serum and show that precise measurement of an array of 29 modified nucleosides in serum by high-performance liquid chromatography with UV scanning with subsequent data modeling may provide a clinically useful approach to patient classification in diagnosis and subsequent therapeutic monitoring.

Biomarkers, Tumor↗
PubMed1986

Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors.

The intraerythrocytic human malaria parasite, Plasmodium falciparum, requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism. Adenosine has been implicated as a major source for intraerythrocytic hypoxanthine production via deamination and phosphorolysis, utilizing adenosine deaminase and purine nucleoside phosphorylase, respectively. To study the expression and characteristics of human malaria purine nucleoside phosphorylase, P. falciparum was successfully cultured in purine nucleoside phosphorylase-deficient human erythrocytes to an 8% parasitemia level. Purine nucleoside phosphorylase activity was undetectable in the uninfected enzyme-deficient host red cells but after parasite infection rose to 1.5% of normal erythrocyte levels. The parasite purine nucleoside phosphorylase was not cross-reactive with antibody against human enzyme, exhibited a calculated native molecular weight of 147,000, and showed a single major electrophoretic form of pI 5.4 and substrate specificity for inosine, guanosine and deoxyguanosine but not xanthosine or adenosine. The Km values for substrates, inosine and guanosine, were 4-fold lower than that for the human erythrocyte enzyme. In these studies we have identified two novel potent inhibitors of both human erythrocyte and parasite purine nucleoside phosphorylase, 8-amino-5'-deoxy-5'-chloroguanosine and 8-amino-9-benzylguanine. These enzyme inhibitors may have some antimalarial potential by limiting hypoxanthine production in the parasite-infected erythrocyte.

Animals↗
PubMed1987

Modified nucleosides in patients with acquired immune deficiency syndrome (AIDS) and individuals at high risk of AIDS: correlations with lymphadenomegaly and immunological parameters.

Patients with certain malignant diseases excrete in their urine elevated levels of modified nucleosides originating predominantly from the breakdown of transfer RNA (tRNA). Acquired immune deficiency syndrome (AIDS), often associated with rapidly progressing Kaposi's sarcoma (KS), is currently occurring in many countries. Male homosexuals are considered to be at highest risk of developing these disorders. We have previously reported that patients with AIDS excrete elevated levels of modified nucleosides. In this communication, we report on modified nucleoside levels measured in 77 male homosexuals without clinical manifestations of AIDS at the time of examination. A high frequency of abnormal nucleoside levels was found in this high-risk group. There was a trend towards higher levels in individuals with lymphadenomegaly, considered a prodrome of AIDS. Statistically significant correlations were found between some of the nucleosides (pseudouridine and dimethylguanosine) and degree of lymphadenomegaly. Pseudouridine, 1-methyl-adenosine and dimethylguanosine were inversely related to percentages of total T-lymphocytes (T11), suppressor T-lymphocytes (T8), and number of natural killer cells (Leu-7). These findings suggest that determination of urinary nucleoside levels may help identify individuals at high risk of developing AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Effect of ischemia on nucleosides and bases in rat liver and hepatoma 3924A.

A high-pressure liquid chromatographic method was developed which achieved a separation and quantitation of 20 biologically important nucleosides and bases. The concentrations of pyrimidine nucleosides and bases, namely deoxycytidine, cytosine, cytidine, uracil, and uridine (22.6, 10.1, 5.2, 2.9, and 2.4 nmol/ml, respectively) were high in plasma, whereas purine nucleosides and bases were present in concentrations less than 2.5 nmol/ml. In erythrocytes, the pools of xanthine, hypoxanthine, and xanthosine were 32-, 27-, and 22-fold larger, respectively, whereas cytidine, uridine, and deoxycytidine were only 21, 12, and 5% of plasma concentrations. The results suggest a compartmental system for transport of some of the purine and pyrimidine nucleosides and bases in the whole blood. Studies on the effect of ischemia on nucleoside and base pools in rat liver indicated marked increases within 30 s in the concentrations of adenine, adenosine, inosine, hypoxanthine, uridine, and xanthine, whereas in hepatoma the effects were less pronounced. By 2 and 5 min ischemia these perturbations were most marked in both liver and hepatoma. These results indicate a need for rapid freeze-clamp preparation of tissue samples to obtain precise and repeatable results in the determination of tissue nucleoside and nucleobase concentrations.

Animals↗
PubMed1978

Purification and characterization of human erythrocyte purine nucleoside phosphorylase and its subunits.

Purine nucleoside phosphorylase (EC 2.4.2.1; purine nucleoside:orthophosphate ribosyltransferase) from fresh human erythrocytes has been purified to homogeneity in two steps with an overall yield of 56%. The purification involves DEAE-Sephadex chromatography followed by affinity chromatography on a column of Sepharose/formycin B. This scheme is suitable for purification of the phosphorylase from as little as 0.1 ml of packed erythrocytes. The native enzyme appears to be a trimer with native molecular weight of 93,800 and the subunit molecular weight of 29,700 +/- 1,100. Two-dimensional gel electrophoresis of the purified enzyme under denaturing conditions revealed four major separable subunits (numbered 1 to 4) with the same molecular weight. The apparent isoelectric points of subunits 1 to 4 in 9.5 M urea are 6.63, 6.41, 6.29, and 6.20, respectively. The different subunits are likely the result of post-translational modification of the enzyme and provide an explanation of the complex native isoelectric focusing pattern of purine nucleoside phosphorylase from erythrocytes. Three of the four subunits are detectable in two-dimensional electrophoretic gels of crude hemolysates. Knowing the location of the subunits of purine nucleoside phosphorylase in a two-dimensional electropherogram allows one to characterize the purine nucleoside phosphorylase in crude cell extracts from individuals with variant or mutant purine nucleoside phosphorylase as demonstrated in a subsequent communication. Partial purification of the phosphorylase from 1 ml of erythrocytes on DEAE-Sephadex increases the sensitivity of detection of the subunits to the 0.3% level.

Erythrocytes↗
PubMed1983

Differential excretion of modified nucleosides in adult acute leukemia.

Excretion of modified nucleosides in urine was measured in 23 adults with acute leukemia to determine correlation of nucleoside excretion with disease activity. In addition, differences in excretion between patients with acute lymphoblastic leukemia (ALL) and patients with acute myeloid leukemia (AML) were established. Six modified nucleosides were resolved and quantitated by reversed-phase high-performance liquid chromatography (HPLC). Patients with ALL at initial diagnosis or in relapse had significantly higher concentrations of 1-methylinosine and N2,N2-dimethylguanosine in their urine compared to patients in remission (p less than 0.01, p less than 0.05, respectively). One patient with ALL was followed with serial nucleoside determinations over a period of 18 mo; nucleoside excretion correlated closely with disease activity. Nucleoside excretion in patients with AML did not change significantly with disease activity. Considering only those patients at initial diagnosis or in relapse, excretion of 1-methylinosine and N2,N2-dimethylguanosine was significantly higher in ALL than in AML (p less than 0.01, p less than 0.05, respectively). Thus, urinary excretion of 1-methylinosine and N2,N2-dimethylguanosine by adults with acute leukemia may prove to be valuable clinically in following disease activity in patients with ALL and in distinguishing patients with ALL from those with AML.

Adenosine↗
PubMed1980

Submolecular characterization of a mutant human purine-nucleoside phosphorylase.

Purine-nucleoside phosphorylase deficiency in humans is associated with a severe defect in thymus-derived lymphocyte function. We have used the consanguineous parents of one purine-nucleoside phosphorylase-deficient patient as a source of mutant protein since the enzyme is totally lacking in the homozygous deficient child. When analyzed by denaturing two-dimensional gel electrophoresis, purified erythrocytic purine-nucleoside phosphorylase from normal individuals has four major and two minor subunits of identical molecular weight (29,700) but different isoelectric points. Similar analysis of phosphorylase purified from the parents of the purine-nucleoside phosphorylase-deficient child reveals the presence of two additional, more alkaline subunits with molecular weights significantly greater (approximately 500) than the normal subunits. Comparison of the two-dimensional thin layer peptide maps of the complete tryptic hydrolysates of the 125I-labeled subunits demonstrates that all eight subunits have a majority of their peptides in common, and thus, the structures of all are closely related. Peptide maps of the major subunits of normal purine-nucleoside phosphorylase are all identical with each other but different in several peptides from those of the normal minor subunits. Peptide maps of the mutant subunits differ from those of the normal major subunits only in the loss of one normal peptide and the presence of two new peptides. Tryptic peptide analysis of overlapping partial proteolytic cleavage fragments of the mutant and normal major subunits of purine-nucleoside phosphorylase has been used to determine the order of the iodinated tryptic peptides in the molecule. These results indicate that the mutant subunits are altered at an internal position rather than at the termini of the protein. A likely explanation of this internal alteration is an insertion of several tandem amino acid residues, perhaps resulting from an unequal genetic crossover or an intron processing abnormality.

Amino Acid Sequence↗
PubMed1981

[Phenotypic manifestation of the pnd mutation, which promotes purine nucleoside cleavage by Escherichia coli K-12 cells, in the genome of strains defective in the metabolism of nucleic acid precursors].

Strains of Escherichia coli K-12 containing both pnd1 mutation, rendering bacteria capable to catabolize purine nucleosides without participation of purine nucleoside phosphorylase (pup gene), and mutations in several genes of purine metabolism or nucleosides catabolism have been constructed. The introduction of the deletion mutation in adenosine deaminase gene (add) into the pup pnd genome does not affect the ability of mutants to utilize adenosine and deoxyadenosine as the sole carbon and energy sources. Mutations affecting purine phosphoribosyltransferases (hpt and gpt) block the ability of pup pnd mutants to utilize hypoxanthine, guanine and their deoxyribonucleosides and also xanthine and xanthosine as the only purine source. A mutation in deoxyribomutase (drm) disturbs the ability of pnd mutants to use all purine ribo- and deoxy-ribonucleosides as carbon and energy sources, whereas a mutation in deoxyriboaldolase (dra) only disturbs utilization of deoxyribonucleosides. These data seem to indicate that the activity promoted by pnd mutations catalyzes the cell reaction of irreversible phosphorolytic cleavage of the N-glycoside bond of the purine nucleosides molecules: purine nucleoside + phosphate leads to purine + pentose-1-phosphate. It is suggested that pnd mutations affect the structural gene of some phosphorolytic enzyme and modify its substrate specificity. Evidence is presented that the structural gene of a new nucleoside phosphorylase is not sensitive to catabolite repression.

Escherichia coli↗