scholarly journals Studies of inhibition of rat spermidine synthase and spermine synthase

1980 ◽  
Vol 187 (2) ◽  
pp. 419-428 ◽  
Author(s):  
Hiroshige Hibasami ◽  
Ronald T. Borchardt ◽  
Shiang Yuan Chen ◽  
James K. Coward ◽  
Anthony E. Pegg
Keyword(s):  
Amino Acid ◽  
Ventral Prostate ◽  
Amino Group ◽  
Spermidine Synthase ◽  
Polyamine Synthesis ◽  
Weak Inhibitor ◽  
Spermine Synthase ◽  
Rat Ventral Prostate ◽  
Potential Inhibitors ◽  
Derivatives Of

1. S-Adenosyl-l-methionine, S-adenosyl-l-homocysteine, 5′-methylthioadenosine and a number of analogues having changes in the base, sugar or amino acid portions of the molecule were tested as potential inhibitors of spermidine synthase and spermine synthase from rat ventral prostate. 2. S-Adenosyl-l-methionine was inhibitory to these reactions, as were other nucleosides containing a sulphonium centre. The most active of these were S-adenosyl-l-ethionine, S-adenosyl-4-methylthiobutyric acid, S-adenosyl-d-methionine and S-tubercidinylmethionine, which were all comparable in activity with S-adenosylmethionine itself, producing 70–98% inhibition at 1mm concentrations. Spermine synthase was somewhat more sensitive than spermidine synthase. 3. 5′-Methylthioadenosine, 5′-ethylthioadenosine and 5′-methylthiotubercidin were all powerful inhibitors of both enzymes, giving 50% inhibition of spermine synthase at 10–15μm and 50% inhibition of spermidine synthase at 30–45μm. 4. S-Adenosyl-l-homocysteine was a weak inhibitor of spermine synthase and practically inactive against spermidine synthase. Analogues of S-adenosylhomocysteine lacking either the carboxy or the amino group of the amino acid portion were somewhat more active, as were derivatives in which the ribose ring had been opened by oxidation. The sulphoxide and sulphone derivatives of decarboxylated S-adenosyl-l-homocysteine and the sulphone of S-adenosyl-l-homocysteine were quite potent inhibitors and were particularly active against spermidine synthase (giving 50% inhibition at 380, 50 and 20μm respectively). 5. These results are discussed in terms of the possible regulation of polyamine synthesis by endogenous nucleosides and the possible value of some of the inhibitory substances in experimental manipulations of polyamine concentrations. It is suggested that 5′-methylthiotubercidin and the sulphone of S-adenosylhomocysteine or of S-adenosyl-3-thiopropylamine may be particularly valuable in this respect.

N-DICHLOROACETYL DERIVATIVES OF SERINE AND THREONINE AND OF THEIR ESTERS AND SODIUM SALTS

1960 ◽  
Vol 38 (7) ◽  
pp. 1135-1140 ◽  
Author(s):  
I. Levi ◽  
A. E. Koller ◽  
G. Laflamme ◽  
J. W. R. Weed
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Antitumor Activity ◽  
Amino Acid Ester ◽  
Amino Group ◽  
Sodium Salts ◽  
Sarcoma 37 ◽  
Walker Carcinoma ◽  
Derivatives Of ◽  
Dichloroacetyl Chloride

The N-dichloroacetyl derivatives of DL-serine and DL-threonine were prepared by the Schotten–Baumann reaction from the amino acids and dichloroacetyl chloride. Negative ninhydrin tests coupled with elementary analyses indicated that only the amino group was acylated. The ester derivatives of these compounds were prepared either by esterification of the N-dichloroacetyl-DL-amino acid with diazomethane or by the reaction of the amino acid ester with dichloroacetyl chloride in the presence of triethylamine. The sodium salts and the esters were tested for antitumor activity against sarcoma 37 in mice and Walker carcinoma 256 in rats. In both cases regression of the tumors was obtained.

Effects of inhibitors of spermidine synthase and spermine synthase on polyamine synthesis in rat tissues

1993 ◽  
Vol 45 (9) ◽  
pp. 1897-1903 ◽  
Author(s):  
Akira Shirahata ◽  
Norio Takahashi ◽  
Takanobu Beppu ◽  
Harumi Hosoda ◽  
Keijiro Samejima
Keyword(s):  
Rat Tissues ◽  
Spermidine Synthase ◽  
Polyamine Synthesis ◽  
Spermine Synthase

scholarly journals Specificity of mammalian spermidine synthase and spermine synthase

1981 ◽  
Vol 197 (2) ◽  
pp. 315-320 ◽  
Author(s):  
A E Pegg ◽  
K Shuttleworth ◽  
H Hibasami
Keyword(s):  
Small Extent ◽  
Spermidine Synthase ◽  
Mouse Fibroblasts ◽  
Spermine Synthase ◽  
Alpha Omega ◽  
Derivatives Of ◽  
Polyamine Derivatives

1. The specificity of rat prostatic spermidine synthase and spermine synthase with respect to the amine acceptor of the propylamine group was studied. 2. Spermidine synthase could use cadaverine (1,5-diaminopentane) instead of putrescine, but the Km for cadaverine was much greater and the rate with 1mM-cadaverine was only 10% of that with putrescine. 1,3-Diaminopropane was even less active (2% of the rate with putrescine) and no other compound tested (including longer alpha, omega-diamines, spermidine and its homologues and monoacetyl derivatives) was active. 3. Spermine synthase was equally specific. The only compounds tested that showed any activity were 1,8-diamino-octane, sym-homospermidine, sym-norspermidine and N-(3-aminopropyl)-cadaverine, which at 1mM gave rates 2, 17, 3 and 4% of the rate with spermidine respectively. 4. The formation of polyamine derivatives of cadaverine and to a very small extent of 1,3-diaminopropane was confirmed by exposing transformed mouse fibroblasts to these diamines when synthesis of putrescine was prevented by alpha-difluoromethylornithine. Under these conditions the cells accumulated significant amounts of N-(3-aminopropyl)cadaverine and NN'-bis(3-aminopropyl)cadaverine when exposed to cadaverine and small amounts of sym-norspermidine and sym-norspermine when exposed to 1,3-diaminopropane.

The Pyoverdin of Pseudomonas fluorescens G173, a Novel Structural Type Accompanied by Unexpected Natural Derivatives of the Corresponding Ferribactin

2003 ◽  
Vol 58 (1-2) ◽  
pp. 1-10 ◽  
Author(s):  
Diana Uría Fernández ◽  
Regine Fuchs ◽  
Mathias Schäfer ◽  
Herbert Budzikiewicz ◽  
Jean-Marie Meyer
Keyword(s):  
Amino Acid ◽  
Pseudomonas Fluorescens ◽  
Condensation Product ◽  
Structural Characteristics ◽  
Structural Type ◽  
Carboxyl Group ◽  
Amino Group ◽  
Acetyl Group ◽  
Derivatives Of ◽  
A New Species

The siderophores produced by Pseudomonas fluorescens G173 are unusual in several respects. So far all pyoverdins with a C-terminal cyclopeptidic substructure have in common that the ε-amino group of an in-chain Lys is bound amidically to the carboxyl group of a C-terminal Ser or Thr and that N5-formyl-N5-hydroxy Orn (FoOHOrn) is the next amino acid after Lys. FoOHOrn may (cyclotetrapeptidic structures) be or may not (cyclotripeptidic structures) be followed by a further amino acid. In the pyoverdin described here Orn instead of Lys is the amino acid forming the cycle, FoOHOrn is replaced by AcOHOrn which does not follow the branching Orn but is the penultimate amino acid and finally the last amino acid is Asp. The producing strain which had been classified as Pseudomonas fluorescens may well be a new species. Pyoverdins are frequently accompanied by ferribactins which are considered to be their biogenetic precursors. They always have the same amino acid chain as the co-occurring pyoverdins but the pyoverdin chromophore is replaced by a condensation product of ʟ-Dab and ᴅ-Tyr with the amino group of Tyr bound to the γ-carboxyl group of Glu. A ferribactin having these structural characteristics is produced by the investigated strain, but it is accompanied by derivatives where the α-amino group of Glu is partially or completely transformed into a hydroxamic acid by substitution with a hydroxyl and/or acetyl group

Synthesis of some 5?-O-amino acid derivatives of uridine as potential inhibitors ofUDP-glucuronosyltransferase

1997 ◽  
Vol 128 (6-7) ◽  
pp. 725-732 ◽  
Author(s):  
D. K. Alargov ◽  
Z. Naydenova ◽  
K. Grancharov ◽  
P. S. Denkova ◽  
E. V. Golovinsky
Keyword(s):  
Amino Acid ◽  
Amino Acid Derivatives ◽  
Potential Inhibitors ◽  
Derivatives Of

scholarly journals Inhibition of the synthesis of polyamines and macromolecules by 5′-methylthioadenosine and 5′-alkylthiotubercidins in BHK21 cells

1982 ◽  
Vol 204 (3) ◽  
pp. 697-703 ◽  
Author(s):  
Aarne Raina ◽  
Kyllikki Tuomi ◽  
Raija-Leena Pajula
Keyword(s):  
Growth Inhibition ◽  
Spermidine Synthase ◽  
Baby Hamster Kidney ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Spermine Synthase ◽  
Target Sites ◽  
Polyamine Content ◽  
Exogenous Spermidine

5′-Methylthioadenosine and four 5′-alkylthiotubercidins were tested for their ability to inhibit polyamine synthesis in vitro and to decrease polyamine concentration and prevent growth of baby-hamster-kidney (BHK21) cells. 5′-Methylthioadenosine and 5′-methylthiotubercidin decreased the activity of spermidine synthase from brain to roughly the same extent, whereas brain spermine synthase was much more strongly inhibited by 5′-methylthioadenosine compared with 5′-methylthiotubercidin. These nucleoside derivatives also inhibited the growth of BHK21 cells and increased the concentration of putrescine. 5′-Methylthioadenosine decreased cellular spermine concentration, whereas 5′-methylthiotubercidin lowered the concentration of spermidine. The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were enhanced in cells grown in the presence of 5′-methylthiotubercidin. The growth inhibition produced by these nucleoside derivatives was not reversed by exogenous spermidine or spermine. 5′-Ethylthiotubercidin, 5′-propylthiotubercidin and 5′-isopropylthiotubercidin did not appreciably inhibit spermidine or spermine synthase in vitro or decrease the cellular polyamine content, but effectively prevented the growth of BHK21 cells. All nucleoside derivatives at concentrations of 0.2–1 mm caused a rapid inhibition of protein synthesis. It is concluded that the growth inhibition produced by 5′-methylthioadenosine and 5′-alkylthiotubercidins was not primarily due to polyamine depletion but other target sites, for instance the cellular nucleotide pool, cell membranes etc. must be considered.

scholarly journals Role of propylamine transferases in hormone-induced stimulation of polyamine biosynthesis

1980 ◽  
Vol 192 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Kirsti Käpyaho ◽  
Hannu Pösö ◽  
Juhani Jänne
Keyword(s):  
Seminal Vesicle ◽  
Ornithine Decarboxylase ◽  
Ovarian Tissue ◽  
Ventral Prostate ◽  
Decarboxylase Activity ◽  
Spermidine Synthase ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Spermine Synthase ◽  
Stimulation Of

The effect of various hormones on the activities of the four enzymes engaged with the biosynthesis of the polyamines has been investigated in the rat. Human choriogonadotropin induced a dramatic, yet transient, stimulation of l-ornithine decarboxylase (EC 4.1.1.17) activity in rat ovary, with no or only marginal changes in the activities of S-adenosyl-l-methionine decarboxylase (EC 4.1.1.50), spermidine synthase (aminopropyltransferase; EC 2.5.1.16) or spermine synthase. A single injection of oestradiol into immature rats maximally induced uterine ornithine decarboxylase at 4h after the injection. This early stimulation of ornithine decarboxylase activity was accompanied by a distinct enhancement of adenosylmethionine decarboxylase activity and a decrease in the activities of spermidine synthase and spermine synthase. In the seminal vesicle of castrated rats, testosterone treatment elicited a striking and persistent stimulation of ornithine decarboxylase and adenosylmethionine decarboxylase activities. The activity of spermidine synthase likewise rapidly increased between the first and the second day after the commencement of the hormone treatment, whereas the activity of spermine synthase remained virtually unchanged during the whole period of observation. Testosterone-induced changes in polyamine formation in the ventral prostate were comparable with those found in the seminal vesicle, with the possible exception of a more pronounced stimulation of spermidine synthase activity. It thus appears that an enhancement in one or both of the propylamine transferase (aminopropyltransferase) activities in response to hormone administration is an indicator of hormone-dependent growth (uterus and the male accessory sexual glands), and is not necessarily associated with non-proliferative hormonal responses, such as gonadotropin-induced luteinization of the ovarian tissue.

scholarly journals Effect of analogues of 5′-methylthioadenosine on cellular metabolism. Inactivation of S-adenosylhomocysteine hydrolase by 5′-isobutylthioadenosine

1983 ◽  
Vol 210 (2) ◽  
pp. 429-435 ◽  
Author(s):  
F Della Ragione ◽  
A E Pegg
Keyword(s):  
Convenient Method ◽  
Cellular Metabolism ◽  
Spermidine Synthase ◽  
Polyamine Synthesis ◽  
Adenosylhomocysteine Hydrolase ◽  
Methylthioadenosine Phosphorylase ◽  
Spermine Synthase ◽  
Irreversible Inhibition

The effects of a number of nucleosides related to 5′-methylthioadenosine on the activities of S-adenosylhomocysteine hydrolase, 5′-methylthioadenosine phosphorylase, spermidine synthase and spermine synthase were investigated. Both 5′-methylthioadenosine and 5′-isobutylthioadenosine gave rise to an enzyme-activated irreversible inhibition of S-adenosylhomocysteine hydrolase, but 5′-methylthiotubercidin (5′-methylthio-7-deaza-adenosine), 5′-deoxy-5′-chloroformycin, 5′-ethylthio-2-fluoro-adenosine and 1,N6-etheno-5′-methylthioadenosine were totally ineffective in producing this inactivation. Of the nucleosides tested, only 5′-methylthioadenosine, 5′-methylthiotubercidin and 5′-isobutylthioadenosine were inhibitory towards the aminopropyltransferases responsible for the synthesis of spermine and spermidine. 5′-Methylthiotubercidin, 5′-deoxy-5′-chloroformycin and 5′-isobutylthioadenosine were inhibitors of the degradation of 5′-methylthioadenosine by 5′-methylthioadenosine phosphorylase, but only 5′-isobutylthioadenosine was also a substrate for this enzyme. These results suggest that the effects of 5′-isobutylthioadenosine of the cell may result from the combination of inhibitory actions on polyamine synthesis, 5′-methylthioadenosine degradation and S-adenosylhomocysteine degradation. The resulting increased concentrations of S-adenosylhomocysteine could bring about inhibition of methyltransferase reactions. A new convenient method for the assay of S-adenosylhomocysteine hydrolase in the direction of synthesis is described.

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