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Inorganic Chemistry Dec 2012The synthesis, characterization, binding to calf thymus DNA, and plasmid DNA photocleavage studies of two ruthenium(II) pteridinylphenanthroline complexes are reported...
The synthesis, characterization, binding to calf thymus DNA, and plasmid DNA photocleavage studies of two ruthenium(II) pteridinylphenanthroline complexes are reported where the new pteridinylphenantholine ligands in these complexes are additions to a larger family designed to resemble DNA bases. [Ru(bpy)(2)(L-keto)](PF(6))(2)1 is synthesized from ligand substitution of Ru(bpy)(2)Cl(2) by 4-keto-pteridino[6,7-f]phenanthroline (L-keto). Increasing the reaction temperature during synthesis of 1 causes a ring scission of the L-keto ligand within the pyrimidine ring yielding a second Ru complex, [Ru(bpy)(2)(L-aap)](PF(6))(2)2 where L-aap is 2-amino-3-amidopyrazino[5,6-f]phenanthroline. The ring cleavage reaction is accompanied by the loss of one carbon in the pyrimidine ring. Complexes 1 and 2 are characterized by (1)H NMR, UV/visible absorption and FT-IR spectroscopies and by cyclic voltammetry, and these results are presented in comparison to the previously reported related complexes [Ru(bpy)(2)(L-allox)](PF(6))(2), [Ru(bpy)(2)(L-amino)](PF(6))(2), and [Ru(bpy)(2)(dppz)](PF(6))(2). In addition, 2 has been structurally characterized by X-ray diffraction. Both 1 and 2 are good intercalators of calf thymus DNA as determined by viscometry and binding constants obtained from absorption titrations. Only the ring-cleaved complex 2 exhibits a high degree of pBR322 plasmid photocleavage in contrast to the other pteridinyl-phenanthroline complexes, which exhibit no plasmid DNA photocleavage. Complex 1, however, decomposes in buffer forming the photocleaver 2, demonstrating that sample age and reactivity can affect observed photocleavage. Complex 2 appears to photocleave DNA through a singlet oxygen mechanism.
Topics: Animals; Cattle; DNA; DNA Cleavage; Ligands; Models, Molecular; Molecular Structure; Organometallic Compounds; Photochemical Processes; Plasmids; Pteridines; Pyridines; Ruthenium
PubMed: 23167624
DOI: 10.1021/ic301219z -
Comparative Biochemistry and... 20236-pyruvoyl-tetrahydropterin synthase (PTPS) is the second key enzyme of the pteridine biosynthetic pathway and it plays vital roles in fish body color formation. In this...
6-pyruvoyl-tetrahydropterin synthase (PTPS) is the second key enzyme of the pteridine biosynthetic pathway and it plays vital roles in fish body color formation. In this study, Ccptps of koi carp (Cyprinus carpio L.) was cloned, identified and characterized. The full-length cDNA of Ccptps was 1140 bp and encodes for 139 amino acids. Multiple alignments revealed that the amino acids sequence of CcPTPS shared the highest identity to that of C. carpio, and Ccptps was clustered with cyprinid fishes in phylogenetic tree. Liver tissues of koi carp exhibited the highest expression of Ccptps, followed by muscle and skin tissues. During early developmental stages, the expression of Ccptps declined from 2 dph to 4 dph, and increased from 4 dph to 12 dph. The expressions of Ccptps in three color-related tissues (skin, scale and caudal fin) of whole red (WR) koi carp were significantly higher than that of whole while (WW) koi carp. Immunohistochemistry results of skin tissues showed that CcPTPS was mainly located in epidermis, stratum compactum of dermis and muscle layer, with the signal intensities in stratum compactum and muscle layer were stronger in WR koi carp compared to WW koi carp. Co-expressions of CcPTPS, CcSPR and CcXDH were detected in skin tissues of WW and WR koi carps, with CcPTPS exhibited stronger signal intensity compared to CcSPR and CcXDH. These findings imply that Ccptps is potentially involved in koi carp body color formation through the pteridine synthesis pathway.
Topics: Animals; Carps; Phylogeny; DNA, Complementary; Amino Acids; Pteridines; Fish Diseases
PubMed: 36400267
DOI: 10.1016/j.cbpb.2022.110814 -
Essays in Biochemistry 2011Trypanosomatid parasitic protozoans of the genus Leishmania are autotrophic for both folate and unconjugated pteridines. Leishmania salvage these metabolites from their... (Review)
Review
Trypanosomatid parasitic protozoans of the genus Leishmania are autotrophic for both folate and unconjugated pteridines. Leishmania salvage these metabolites from their mammalian hosts and insect vectors through multiple transporters. Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. PTR1 can act as a metabolic bypass of DHFR inhibition, reducing the effectiveness of existing antifolate drugs. Leishmania possess a reduced set of folate-dependent metabolic reactions and can salvage many of the key products of folate metabolism from their hosts. For example, they lack purine synthesis, which normally requires 10-formyltetrahydrofolate, and instead rely on a network of purine salvage enzymes. Leishmania elaborate at least three pathways for the synthesis of the key metabolite 5,10-methylene-tetrahydrofolate, required for the synthesis of thymidylate, and for 10-formyltetrahydrofolate, whose presumptive function is for methionyl-tRNAMet formylation required for mitochondrial protein synthesis. Genetic studies have shown that the synthesis of methionine using 5-methyltetrahydrofolate is dispensable, as is the activity of the glycine cleavage complex, probably due to redundancy with serine hydroxymethyltransferase. Although not always essential, the loss of several folate metabolic enzymes results in attenuation or loss of virulence in animal models, and a null DHFR-TS mutant has been used to induce protective immunity. The folate metabolic pathway provides numerous opportunities for targeted chemotherapy, with strong potential for 'repurposing' of compounds developed originally for treatment of human cancers or other infectious agents.
Topics: Amino Acid Oxidoreductases; Animals; Carrier Proteins; Folic Acid; Host-Parasite Interactions; Iron-Sulfur Proteins; Leishmania; Metabolic Networks and Pathways; Methionine; Multienzyme Complexes; Pteridines; Purines; Tetrahydrofolate Dehydrogenase; Tetrahydrofolates; Thymidylate Synthase; Transferases
PubMed: 22023442
DOI: 10.1042/bse0510063 -
Proceedings of the National Academy of... Sep 2004Plants are the main source of folate in human diets, but many fruits, tubers, and seeds are poor in this vitamin, and folate deficiency is a worldwide problem. Plants...
Plants are the main source of folate in human diets, but many fruits, tubers, and seeds are poor in this vitamin, and folate deficiency is a worldwide problem. Plants synthesize folate from pteridine, p-aminobenzoate (PABA), and glutamate moieties. Pteridine synthesis capacity is known to drop in ripening tomato fruit; therefore, we countered this decline by fruit-specific overexpression of GTP cyclohydrolase I, the first enzyme of pteridine synthesis. We used a synthetic gene based on mammalian GTP cyclohydrolase I, because this enzyme is predicted to escape feedback control in planta. This engineering maneuver raised fruit pteridine content by 3- to 140-fold and fruit folate content by an average of 2-fold among 12 independent transformants, relative to vector-alone controls. Most of the folate increase was contributed by 5-methyltetrahydrofolate polyglutamates and 5,10-methenyltetrahydrofolate polyglutamates, which were also major forms of folate in control fruit. The accumulated pteridines included neopterin, monapterin, and hydroxymethylpterin; their reduced forms, which are folate biosynthesis intermediates; and pteridine glycosides not previously found in plants. Engineered fruit with intermediate levels of pteridine overproduction attained the highest folate levels. PABA pools were severely depleted in engineered fruit that were high in folate, and supplying such fruit with PABA by means of the fruit stalk increased their folate content by up to 10-fold. These results demonstrate that engineering a moderate increase in pteridine production can significantly enhance the folate content in food plants and that boosting the PABA supply can produce further gains.
Topics: Aldehyde-Lyases; Amino Acid Sequence; Base Sequence; Chemical Engineering; DNA, Complementary; Folic Acid; Fruit; Genetic Vectors; Molecular Sequence Data; Open Reading Frames; Pteridines
PubMed: 15365185
DOI: 10.1073/pnas.0404208101 -
The Journal of Biological Chemistry Jan 1993Stimulation of nitric oxide (NO) synthase in endothelial cells by Ca2+ influx leads to increased intracellular levels of cGMP. NO synthase from various sources is known...
Stimulation of nitric oxide (NO) synthase in endothelial cells by Ca2+ influx leads to increased intracellular levels of cGMP. NO synthase from various sources is known to use tetrahydrobiopterin, flavins, and NADPH as cofactors. We studied the effect of interferon-gamma, tumor necrosis factor-alpha, and lipopolysaccharide on tetrahydrobiopterin biosynthetic activities in human umbilical vein endothelial cells (HUVEC). These stimuli led to an up to 40-fold increase of GTP cyclohydrolase I (EC 3.5.4.16) activity and to increased accumulation of neopterin and tetrahydrobiopterin in HUVEC. Further enzyme activities of tetrahydrobiopterin biosynthesis, i.e. 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase (EC 1.1.1.153), remained unchanged. NO synthase activity in protein fractions from homogenates of cells treated with interferon-gamma plus tumor necrosis factor-alpha was not influenced as compared with untreated controls. However, interferon-gamma alone or in combination with tumor necrosis factor-alpha significantly increased intracellular cGMP formation in intact HUVEC by 50 and 80%, respectively. These stimuli increased intracellular tetrahydrobiopterin concentrations up to 14-fold. NO-triggered cGMP formation was similarly increased by incubation of otherwise untreated cells with sepiapterin, leading to elevated intracellular tetrahydrobiopterin levels. Thus, cytokines indirectly stimulate the activity of constitutive NO synthase in HUVEC by upregulating production of the cofactor tetrahydrobiopterin.
Topics: Amino Acid Oxidoreductases; Biopterins; Cells, Cultured; Cyclic GMP; Endothelium, Vascular; GTP Cyclohydrolase; Humans; Hypoxanthines; Interferon-gamma; Lipopolysaccharides; Neopterin; Nitric Oxide; Nitric Oxide Synthase; Pteridines; Pterins; Tumor Necrosis Factor-alpha; Umbilical Veins
PubMed: 7678411
DOI: No ID Found -
Zeitschrift Fur Naturforschung. Teil B.... Mar 1972
Topics: Animals; Carcinoma, Squamous Cell; Chloramphenicol; Female; Humans; Male; Neoplasm Transplantation; Propylene Glycols; Pteridines; Rats; Rats, Inbred Strains; Riboflavin; Skin Neoplasms; Submandibular Gland; Transplantation, Heterologous; Xanthopterin
PubMed: 4402631
DOI: 10.1515/znb-1972-0313 -
Nature Mar 1964
Topics: Animals; Butterflies; Chromatography; Electrophoresis; Insecta; Pigmentation; Pteridines; Pterins; Research; Ultraviolet Rays; Wings, Animal
PubMed: 14151418
DOI: 10.1038/2011326b0 -
Naunyn-Schmiedeberg's Archives of... Feb 2019Pteridines are bicyclic heterocyclic compounds with a pyrazino[2,3-d]pyrimidine nucleus that have shown a wide range of therapeutic utilities. Concretely,...
Pteridines are bicyclic heterocyclic compounds with a pyrazino[2,3-d]pyrimidine nucleus that have shown a wide range of therapeutic utilities. Concretely, 4-aminopteridine derivatives have demonstrated both anti-inflammatory and anti-cancer properties, and some of them, such as methotrexate, are profusely used in medical practice. We have recently synthesized and tested the biological activity of a novel series of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines, finding that they present anti-inflammatory properties, as they were able to inhibit in vitro the production of pro-inflammatory cytokines TNF-α and IL-6. Now, we have evaluated the anti-tumor potential of these compounds on HL-60 and K562 leukemia cell lines. Cells growing at exponential rate were exposed to decreasing doses of each compound, from 50 to 0.39 μM, for 24, 48, and 72 h. Cell viability was tested by MTT assay and cell death fashion determined by annexin V/propidium iodide assay. The cytotoxicity of the compounds was determined in differentiated macrophage-like HL-60 cells and in human peripheral blood mononuclear cells to evaluate the potential side effects on quiescent tumor cells and normal cells, respectively. Among the series, compounds 1a, 1b, 1g, 1j, and 1k showed anti-proliferative activity. Compounds 1j and 1k were active against both HL-60 and K562 cells, with a lower IC against HL-60 cells. Compounds 1a, 1b, and 1g had a great cytotoxic activity against HL-60, but they were far less potent against K562 cells. None had side effects in differentiated tumor cells or in human peripheral blood mononuclear cells. In conclusion, our results demonstrate that some compounds of this series of 4-amino-2-aryl-6,9-dichlorobenzo[g]pteridines have anti-cancer properties in vitro.
Topics: Antineoplastic Agents; HL-60 Cells; Humans; K562 Cells; Leukemia; Leukocytes, Mononuclear; Pteridines
PubMed: 30465054
DOI: 10.1007/s00210-018-1587-0 -
The Journal of Biological Chemistry Jun 2000In the zebrafish, the peripheral neurons and the pigment cells are derived from the neural crest and share the pteridine pathway, which leads either to the cofactor...
In the zebrafish, the peripheral neurons and the pigment cells are derived from the neural crest and share the pteridine pathway, which leads either to the cofactor tetrahydrobiopterin or to xanthophore pigments. The components of the pteridine pattern were identified as tetrahydrobiopterin, sepiapterin, 7-oxobiopterin, isoxanthopterin, and 2,4,7-trioxopteridine. The expression of GTP cyclohydrolase I activity during the first 24-h postfertilization, followed by 6-pyruvoyl-5,6,7,8-tetrahydropterin synthase and sepiapterin reductase, suggest an early supply of tetrahydrobiopterin for neurotransmitter synthesis in the neurons and for tyrosine supply in the melanophores. At 48-h postfertilization, sepiapterin formation branches off the de novo pathway of tetrahydrobiopterin synthesis. Sepiapterin, via 7,8-dihydrobiopterin and biopterin, serves as a precursor for the formation of 7-oxobiopterin, which may be further catabolized to isoxanthopterin and 2,4,7-trioxopteridine. Neither 7, 8-dihydrobiopterin nor biopterin is a substrate for xanthine oxidoreductase. In contrast, both of these compounds are oxidized at C-7 by a xanthine oxidase variant form, which is inactivated by KCN, but is insensitive to allopurinol. The oxidase and the dehydrogenase form of xanthine oxidoreductase as well as the xanthine oxidase variant have specific developmental patterns. It follows that GTP cyclohydrolase I, the formation of sepiapterin, and the xanthine oxidoreductase family control the pteridine pathway in the zebrafish.
Topics: Alcohol Oxidoreductases; Animals; Chromatography, High Pressure Liquid; GTP Cyclohydrolase; Phosphorus-Oxygen Lyases; Pteridines; Xanthine Dehydrogenase; Zebrafish
PubMed: 10770954
DOI: 10.1074/jbc.M910307199 -
Methods in Enzymology 2008This chapter is focused on the fluorescent pteridine guanine analogs, 3MI and 6MI and on the pteridine adenine analog, 6MAP. A brief overview of commonly used methods to...
This chapter is focused on the fluorescent pteridine guanine analogs, 3MI and 6MI and on the pteridine adenine analog, 6MAP. A brief overview of commonly used methods to fluorescently label oligonucleotides reveals the role the pteridines play in the extensive variety of available probes. We describe the fluorescence characteristics of the pteridine probes as monomers and incorporated into DNA and review a variety of applications including changes in fluorescence intensity, anisotropies, time resolved studies, two photon excitation and single molecule detection.
Topics: Fluorescent Dyes; Nucleic Acids; Pteridines; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Temperature
PubMed: 19152862
DOI: 10.1016/S0076-6879(08)03410-1