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At least 19 recordsLinked to original sources
PubMed1995

Genetic recombination and DNA transpositions induced by pteridines and extracts of pteridine-treated diapausing chrysalids and mutants injected in Drosophila melanogaster.

This paper presents the results of two different treatments using pteridines in Drosophila melanogaster larvae: injection of pteridines alone; and injection of extracts from diapaused Pieris brassicae chrysalids treated with pteridines. Genetic analysis reveals first the induction of lethal or visible recessive mutations that give rise mostly to developmental mutants with variable phenotypes, and second the induction of genetic recombinations. Both treatments disturb genetic recombination in F1 female female issued from the treated larvae. This disturbance is evidenced by the increase in the rate of recombination particularly in the centromere region, and induces in F1 female female and male male clusters of mitotic recombinations of premeiotic origin. These two observations present an analogy with hybrid dysgenesis in the P-M system. This suggests that the treatments either promote the mobility of transposons in female and male larvae and their progeny, or affect the system controlling transposon mobility and integration at specific chromosomal sites. We used in situ hybridization to test our hypotheses, using P, I and copia-like probes. P yields a positive response both at the level of gonadal sterility (gonadal dysgenesis test) and in situ hybridization: after treatment, Oregon K and the wing-altered mutant bspw exhibit a normal number of P elements whereas the maternal strain Oregon K is totally devoid of P. This mutant bspw carries the neutral strain Q (a variant of P), which cannot produce P-M dysgenesis. The implication of these findings for understanding the mode of action of pteridines is twofold: (1) pteridines may be mutagenic agents which perturb meiotic and mitotic recombination; and (2) pteridines disturb the system regulating the mobility and insertion of P elements.

Animals↗
PubMed1997

The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate synthase in pteridine metabolism in the protozoan parasite Leishmania major.

Trypanosomatid protozoans depend upon exogenous sources of pteridines (pterins or folates) for growth. A broad spectrum pteridine reductase (PTR1) was recently identified in Leishmania major, whose sequence places it in the short chain alcohol dehydrogenase protein family although its enzymatic activities resemble dihydrofolate reductases. The properties of PTR1 suggested a role in essential pteridine salvage as well as in antifolate resistance. To prove this, we have characterized further the properties and relative roles of PTR1 and dihydrofolate reductase-thymidylate synthase in Leishmania pteridine metabolism, using purified enzymes and knockout mutants. Recombinant L. major and Leishmania tarentolae, and native L. major PTR1s, were tetramers of 30-kDa subunits and showed similar catalytic properties with pterins and folates (pH dependence, substrate inhibition with H2pteridines). Unlike PTR1, dihydrofolate reductase-thymidylate synthase showed weak activity with folate and no activity with pterins. Correspondingly, studies of ptr1(-) and dhfr-ts- mutants implicated only PTR1 in the ability of L. major to grow on a wide array of pterins. PTR1 exhibited 2000-fold less sensitivity to inhibition by methotrexate than dihydrofolate reductase-thymidylate synthase, suggesting several mechanisms by which PTR1 may compromise antifolate inhibition in wild-type Leishmania and lines bearing PTR1 amplifications. We incorporate these results into a comprehensive model of pteridine metabolism and discuss its implications in chemotherapy of this important human pathogen.

Animals↗
PubMed1977

Oxidation of methyl derivatives of pteridin-4-one, lumazine and related pteridines by bovine milk xanthine oxidase.

1. Pteridin-4-ones, methylated at nitrogen or carbon, N-methylated lumazines and related oxopteridines were studied as substrates of a highly purified bovine milk xanthine oxidase (xanthine : oxygen oxidoreductase, EC 1.2.3.2). 2. The enzyme can oxidise at high rates both uncharged and anionic substrates. Variation of enzymic activity with pH is mainly due to pH-dependent changes in the active enzymic center. 3. Milk xanthine oxidases at different stages of purification convert pteridin-4-one into the 4,7-dione (compound 13 in this article). 4. Methylation at C-6 in the pyrazine moiety enhances enzymic attack at C-2 in the pyrimidine ring. N-Methylation may increase or reduce rates of oxidation. 5. For oxidation at C-2, the most favorable form of the substrate bears a double bond at C(2) = N(3). Attack at C-7 is enhanced strongly in structures bearing a double bond at C(6) = C(7). 6. In general, pteridines react with xanthine oxidase as non-hydrated molecules. However, oxidation of 8-methyllumazine at C-7 may take place by dehydrogenation of the 7-CHOH group of the covalently hydrated molecule.

Animals↗
PubMed1977

Pteridines. 41. Synthesis and dihydrofolate reductase inhibitory activity of some cycloalka[g]pteridines.

A number of homologous 2,4-diaminocycloalka[g]pteridines varying in ring size from 5 to 15 were prepared by (a) condensation of aminomalononitrile tosylate with alpha-oximinocycloalkanones, deoxygenation of the resulting 2-amino-3-cyanocycloalka[b]pyrazine 1-oxides, and guanidine cyclization; (b) guanidine cyclization of the above pyrazine 1-oxides to give 2,4-diaminocycloalka[g]pteridine 8-oxides, followed by deoxygenation; or (c) condensation of 2,4,5,6-tetraaminopyrimidine with a cycloalka-1,2-dione (for the cyclohepta- and cycloocta[g]pteridines only). These compounds were examined for their activity as dihydrofolate reductase inhibitors against Lactobacillus casei, rat liver, L1210, and Trypanosoma cruzi. Activity was found to depend upon ring size, with the greatest activity exhibited by the cyclododeca derivatives 31.

Animals↗
PubMed1980

A survey of the location, isolation and identification of indoles, pteridines and some unknown active substances in sheep pineals. The possible significance of pteridines for the neuroendocrine control of neoplastic growth.

Several indoles with mass spectra identical to those of synthetic melatonin, 5-hydroxyindole-3-acetic acid (5-HIAA), 5-methoxyindole-3-acetic acid (5-MIAA), 5-hydroxytryptophol (5-HTL) and 5-methoxytryptophol (5-MTL) could be located, isolated and identified in sheep pineal extracts using rather simple and mild extraction and separation methods. An antigonadotropin, which differs from melatonin, was isolated and partially purified from sheep pineals, using compensatory ovarian hypertrophy after unilateral ovariectomy as a bioassay. Antigonadotropic and gonadotropic compounds which differ from the indoles above mentioned could be located with the same methods. In vitro, these fractions act either on the hypothalamus or on the anterior pituitary. From the paper chromatography fraction, acting on the anterior pituitary in vitro, a compound could be isolated which is most probably identical with biopterin. In our opinion, however, this compound is not responsible for the antigonadotropic activity of the fraction, observed in vitro. Some pineal fractions showing an effect on the activity of the hypothalamus or anterior pituitary of male rats and mice in vitro, may be also active in some experimental tumour models. A possible relationship between disorders in pteridine metabolism and neoplastic growth is discussed.

Animals↗