Synthesis of 2-Deoxy-β-D-ribonucleosides and 2,3-Dideoxy-β-D-pentofuranosides on Immobilized Bacterial Cells

1994 ◽  
Vol 59 (10) ◽  
pp. 2303-2330 ◽  
Author(s):  
Ivan Votruba ◽  
Antonín Holý ◽  
Hana Dvořáková ◽  
Jaroslav Günter ◽  
Dana Hocková ◽  
...  
Keyword(s):  
The Other ◽  
Bacterial Cells ◽  
Amino Groups ◽  
E Coli ◽  
Pyrimidine Series ◽  
Acceptor Activity ◽  
Dependent Strain ◽  
Pyrimidine Bases ◽  
Heterocyclic Bases ◽  
Derivatives Of

Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs. All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N9-isomers in the purine and N1-isomers in the pyrimidine series. Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety. The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N7-nitrogen atom. On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives. Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed. The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-dideoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-dideoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.

Evolution of the phenomenon of drug-resistance. II. Studies of the extracellular and intracellular derivatives of folic acid in relation to resistance to sulphathiazole and growth factor requirements

1960 ◽  
Vol 153 (951) ◽  
pp. 205-219 ◽  
Keyword(s):  
Folic Acid ◽  
Growth Factor ◽  
Resistant Strain ◽  
Sensitive Strain ◽  
Vitamin B ◽  
Intracellular Accumulation ◽  
E Coli ◽  
Dependent Strain ◽  
Resistant Strains ◽  
Derivatives Of

This study is a continuation of the results published previously (Sevag & Ishii 1958). It surveys quantitatively the extracellular and intracellular accumulation of p -aminobenzoic acid (PAB), pteridine, folic acid (FA) and citrovorum factor (CF) of the various sulphathiazole (ST)-sensitive and ST-resistant strains of Escherichia coli grown with and without ST. The altered enzymic activities of the resistant strain with respect to growth factor requirement is also determined. The following observations are made. The utilization of the exogenous PAB by the PAB-dependent strain is followed by the multiplication of cells. These events are followed by the extracellular accumulation of FA first and then CF. This pattern applies to other strains of E. coli and is in accordance with the well-known sequence of steps involved in the synthesis of PAB, pteridine, FA, CF and growth. It is shown that PAB accumulates principally extracellularly, and pteridine principally intracellularly. The synthesis of FA by the resistant strain is at least tenfold more resistant to ST than in the sensitive strain. In the resistant strain there is a greater intracellular than extracellular accumulation of FA and CF. In the sensitive strain this relationship is reversed. The resistant strains are inheritably capable of synthesizing greater amounts of pteridine, FA and CF. The PAB-dependent ST-sensitive strain can utilize a combination of 1-methionine and any of the purines, of 1-methionine alone, or vitamin B 12 alone in place of PAB for a partial or full growth. The related resistant strain, on the other hand, is unable to multiply in the salts-glucose medium with and without PAB. It requires a combination of 1-methionine and glycine for growth which cannot be replaced by any of the factors mentioned above. This requirement of the resistant strain for growth is analyzed as a deficiency of the enzymic transmethylations and transhydroxymethylation involving the function of CF in the resistant strain.

Syntheses of Enantiomeric N-(3-Hydroxy-2-phosphonomethoxypropyl) Derivatives of Purine and Pyrimidine Bases

1993 ◽  
Vol 58 (3) ◽  
pp. 649-674 ◽  
Author(s):  
Antonín Holý
Keyword(s):  
Benzoyl Chloride ◽  
Sodium Hydride ◽  
Cesium Carbonate ◽  
Amino Groups ◽  
Heterocyclic Base ◽  
Pyrimidine Bases ◽  
Derivatives Of ◽  
General Method

Methods of preparation of N-(3-hydroxy-2-phosphonomethoxypropyl) (HPMP) derivatives of (2S)- and (2R)-configuration (compounds I and XXVII, respectively) are described. The general method starts from the corresponding N-(2,3-dihydroxypropyl) derivatives which were converted either into the (R)-enantiomers XIII by reaction of the base with (R)-glycidol butyrate (XII) in the presence of cesium carbonate and subsequent methanolysis, or into the (S)-enantiomers XI by alkylation of the base with (R)-2,2-dimethyl-4-tosyloxymethyl-1,3-dioxolane (V) in the presence of the same reagent. The amino groups on the heterocyclic base in compounds XI and XIII were benzoylated by silylation followed by reaction with benzoyl chloride and the obtained N-benzoates XV and XVII on reaction with trityl chloride afforded the corresponding 3'-O-trityl derivatives XVI and XVIII. These compounds were condensed with bis(2-propyl) p-sulfonyloxymethylphosphonate (XXIII) in dimethylformamide in the presence of sodium hydride to give the fully protected diesters XXIV and XXVIII. These compounds could be selectively acid-hydrolyzed to remove the trityl group only under formation of compounds XXXV, or methanolyzed and then acid-hydrolyzed to remove the trityl and N-benzoyl groups and lead to compounds XXVI and XXX, or treated with bromotrimethylsilane to remove the trityl and 2-propyl group to give phosphonates of the type XXXI. All the three types of compounds were then converted into free phosphonates of the (S)-series (I) and the (R)-series (XXVII). Derivatives of cytosine (Ia, XXVIIa), adenine (Ib, XXVIIb), 2,6-diaminopurine (Ic, XXVIIc) and guanine (Id, XXVIId) were prepared. Condensation of the partially blocked adenine deriavtive XXXV with the tosyl derivative XXIII and subsequent deprotection afforded 9-(S)-(2,3-diphosphonomethoxy propyl)adenine (XLIII). Reaction of the same compound XXXV or its (R)-enantiomer XXXVIII with diethyl phosphonate , followed by deblocking, afforded 3'-O-phosphoryl derivatives (S)-HPMPA (XXXVII) and (R)-HPMPA (XL).

scholarly journals Yeast Bax Inhibitor (Bxi1p/Ybh3p) is a Calcium Channel in E. coli

2019 ◽  
Author(s):  
James Mullin ◽  
John Kalhorn ◽  
Nicholas Mello ◽  
Amanda Raffa ◽  
Alexander Strakosha ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Saccharomyces Cerevisiae ◽  
Calcium Channel ◽  
The Other ◽  
Bacterial Cells ◽  
E Coli ◽  
Founding Member ◽  
Bona Fide ◽  
Small Molecular Inhibitors

AbstractHuman Bax Inhibitor-1 (HsBI-1/TMBIM6) is the founding member of the evolutionary conserved TMBIM superfamily of proteins that share sequence homology within the transmembrane Bax inhibitor-containing motif (TMBIM). Mechanistically, BI-1/TMBIM6 and all the other mammalian TMBIM proteins appear to be involved in the maintenance of calcium homeostasis, and the crystal structure of a bacterial TMBIM protein, BsYetJ, suggests that the protein is a pH-sensitive calcium leak. The budding yeast, Saccharomyces cerevisiae, has a single TMBIM family member (YNL305C) named Bxi1p/Ybh3p. To determine the function of Bxi1p/Ybh3p, we overexpressed Bxi1p-EGFP in E. coli to determine if it is a calcium channel. We show that bacterial cells expressing Bxi1p-EGFP are more permeable to calcium than controls. Thus, our data suggests that yeast Bax inhibitor (Bxi1p) is a calcium channel in E. coli, lending support to our proposal that Bxi1p is a bona fide member of the TMBIM family of proteins. Further, we use our bacterial system to show that gadolinium is an inhibitor of Bxi1p in vivo, suggesting a path forward to identifying other small-molecular inhibitors of this clinically-important and highly conserved superfamily of proteins. Finally, parallel experiments revealed that the human Bax Inhibitor-1 (HsBI-1/TMBIM6) is also a calcium channel in bacteria that can be inhibited by gadolinium.

Synthesis of N-(2-(2-phosphonylethoxy)ethyl) derivatives of heterocyclic bases

1990 ◽  
Vol 55 (3) ◽  
pp. 809-818 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Rosenberg ◽  
Hana Dvořáková
Keyword(s):  
Triethyl Phosphite ◽  
Sodium Salts ◽  
Subsequent Hydrolysis ◽  
Pyrimidine Bases ◽  
Heterocyclic Bases ◽  
Derivatives Of

Reaction of bis(2-chloroethyl) ether (II) with triethyl phosphite afforded diethyl 2-chloroethoxyethylphosphonate (III). This compound reacts with sodium salts of heterocyclic bases to give diethyl esters of N-(2-(2-phosphonylethoxy)ethyl) derivatives of purine and pyrimidine bases IV. Compounds IV on reaction with bromotrimethylsilane and subsequent hydrolysis were converted into N-(2-(phosphonylethoxy)ethyl) derivatives IV.

Synthesis of N-(2-phosphonylmethoxyethyl) derivatives of heterocyclic bases

1989 ◽  
Vol 54 (8) ◽  
pp. 2190-2210 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Rosenberg ◽  
Hana Dvořáková
Keyword(s):  
Alkali Metal ◽  
Metal Salts ◽  
Alkali Metal Salts ◽  
Phosphonic Acids ◽  
Pyrimidine Bases ◽  
Methyl Derivatives ◽  
Heterocyclic Bases ◽  
Derivatives Of

The preparation of N-(2-phosphonylmethoxyethyl) derivatives of purine and pyrimidine bases, IV, as analogs of the antiviral 9-(2-phosphonylmethoxyethyl)adenine (PMEA, I), is described. The synthesis consists in alkylation of alkali metal salts of heterocyclic bases or their N- or O-substituted derivatives with diethyl 2-p-toluenesulfonyloxyethoxymethylphosphonate (IIa), 2-chloroethoxymethylphosphonate (IIb) or 2-bromoethoxymethylphosphonate (IIc). The obtained N-(2-diethoxyphosphonylmethoxyethyl) derivatives of heterocyclic bases (III) were treated with bromotrimethylsilane to give phosphonic acids IV. Compounds IV were prepared from pyrimidines (uracil, cytosine and their 5-methyl derivatives), purines (adenine and its N6- and C(2)-substituted derivatives, hypoxanthine, guanine, 6-hydrazinopurine and 6-methylthiopurine etc.) and their analogs (3-deazaadenine etc.).

Synthesis of Isomeric N-(3-Fluoro-2-hydroxypropyl) and N-(2-Fluoro-3-hydroxypropyl) Derivatives of Purine and Pyrimidine Bases

1992 ◽  
Vol 57 (7) ◽  
pp. 1466-1482 ◽  
Author(s):  
Jindřich Jindřich ◽  
Hana Dvořáková ◽  
Antonín Holý
Keyword(s):  
Hydrogen Fluoride ◽  
Potassium Carbonate ◽  
Sodium Salt ◽  
Methyl Derivative ◽  
Chloro Derivative ◽  
Pyrimidine Bases ◽  
Heterocyclic Bases ◽  
Hydrolysis Of ◽  
Derivatives Of ◽  
Subsequent Acid

Reaction of fluoromethyloxirane (III) with heterocyclic bases in the presence of potassium carbonate afforded N-(3-fluoro-2-hydroxypropyl) derivatives of adenine (VI), 3-deazaadenine (VII), 2-amino-6-chloropurine (XII), 6-nitro-1-deazapurine (IX), 4-methoxy-2-pyrimidone (XVIII) and its 5-methyl derivative (XIX). Acid hydrolysis of compounds XII, XVIII, and XIX gave 9-(3-fluoro-2-hydroxypropyl)guanine (XIII), 1-(3-fluoro-2-hydroxypropyl)uracil (XX) and -thymine (XXI). The intermediates XVIII and XIX were ammonolyzed to give 1-(3-fluoro-2-hydroxypropyl)cytosine (XXII) and -5-methylcytosine (XXIII). Reaction of chloro derivative XII with sodium azide followed by hydrogenation of the formed 2-amino-6-azidopurine (XIV) led to 9-(3-fluoro-2-hydroxypropyl)-2,6-diaminopurine (XV). 9-(3-Fluoro-2-hydroxypropyl)-1-deazaadenine (X) was obtained by hydrogenation of compound IX. Benzyloxymethyloxirane (XXIV) was reacted with pyridine-hydrogen fluoride adduct to give 3-benzyloxy-2-fluoropropanol (XXV) whose tosylate XXVI on reaction with sodium salt of adenine and subsequent hydrogenolysis of the intermediate XXVII afforded 9-(2-fluoro-3-hydroxypropyl)adenine (XXVIII). The same compound was obtained by reaction of 3-benzyloxy-1-bromo-2-fluoropropanol (XXX) with sodium salt of adenine followed by methanolysis. Condensation of sodium salt of XI, XVI, and XVII with synthon XXX and subsequent acid deblocking gave 9-(2-fluoro-3-hydroxypropyl)guanine (XXXIII), 1-(2-fluoro-3-hydroxypropyl)uracil (XXXVI), and 1-(2-fluoro-3-hydroxypropyl)thymine (XXXVII). 1-(2-Fluoro-3-hydroxypropyl) derivatives of cytosine (XXXVIII) and 5-methylcytosine (XXXIX) were obtained by ammonolysis of the corresponding 4-methoxypyrimidine intermediates XXXIV and XXXV.

Synthesis of N-(3-Fluoro-2-phosphonomethoxypropyl) (FPMP) Derivatives of Heterocyclic Bases

1993 ◽  
Vol 58 (7) ◽  
pp. 1645-1667 ◽  
Author(s):  
Jindřich Jindřich ◽  
Antonín Holý ◽  
Hana Dvořáková
Keyword(s):  
Heterocyclic Ring ◽  
Hydroxyl Group ◽  
Subsequent Removal ◽  
Heterocyclic Base ◽  
Primary Hydroxyl ◽  
Pyrimidine Bases ◽  
Ether Treatment ◽  
Heterocyclic Bases ◽  
Derivatives Of ◽  
Chiral Synthon

A new group of compounds has been prepared: N-(3-fluoro-2-phosphonomethoxypropyl) (FPMP) derivatives of purine and pyrimidine bases which exhibit a significant selective activity against a broad spectrum of retroviruses. Racemic N-(3-fluoro-2-phosphonomethoxypropyl) derivatives of adenin (V), guanine (IX), cytosine (XIII), 2,6-diaminopurine (XXI), 3-deazaadenin e(XVII), xanthine (X) and hypoxanthin (VI) were prepared from the corresponding N-(3-fluoro-2-hydroxypropyl) derivatives after protection of amino group at the heterocyclic ring by selective benzoylation, reaction with diisopropyl p-toluenesulfonyloxymethylphosphonate (II), and subsequent removal of the protecting groups. Chiral FPMP derivatives were prepared by reaction of heterocyclic base with the corresponding chiral synthon (XXX, XXXVII) followed by deprotection. The required chiral synthons were obtained from enantiomeric 3-fluoro-1,2-propanediols by two methods. In the first, the primary hydroxyl group was tritylated, the obtained derivative was reacted with compound II, the trityl group was removed and the product was mesylated to give synthon XXXVII. The second pathway consisted in selective tosylation of the primary hydroxyl group and conversion of the secondary hydroxyl into the acetoxymethyl ether via the methoxymethyl ether; treatment of the acetoxy compound with bromotrimethylsilane and triisopropyl phosphite afforded the desired synthon XXX.

scholarly journals Suppression of Escherichia coli Growth Dynamics via RNAs Secreted by Competing Bacteria

2021 ◽  
Vol 8 ◽  
Author(s):  
Natalia Markelova ◽  
Olga Glazunova ◽  
Olga Alikina ◽  
Valeriy Panyukov ◽  
Konstantin Shavkunov ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Rhodospirillum Rubrum ◽  
Growth Dynamics ◽  
The Other ◽  
Bacterial Cells ◽  
E Coli ◽  
Short Rnas ◽  
General Terms ◽  
Coli Growth

With the discovery of secreted RNAs, it has become apparent that the biological role of regulatory oligonucleotides likely goes beyond the borders of individual cells. However, the mechanisms of their action are still comprehended only in general terms and mainly for eukaryotic microRNAs, which can interfere with mRNAs even in distant recipient cells. It has recently become clear that bacterial cells lacking interference systems can also respond to eukaryotic microRNAs that have targets in their genomes. However, the question of whether bacteria can perceive information transmitted by oligonucleotides secreted by other prokaryotes remained open. Here we evaluated the fraction of short RNAs secreted by Escherichia coli during individual and mixed growth with Rhodospirillum rubrum or Prevotella copri, and found that in the presence of other bacteria E. coli tends to excrete oligonucleotides homologous to alien genomes. Based on this observation, we selected four RNAs secreted by either R. rubrum or P. copri, together with one E. coli-specific oligonucleotide. Both fragments of R. rubrum 23S-RNA suppressed the growth of E. coli. Of the two fragments secreted by P. copri, one abolished the stimulatory effect of E. coli RNA derived from the 3′-UTR of ProA mRNA, while the other inhibited bacterial growth only in the double-stranded state with complementary RNA. The ability of two RNAs secreted by cohabiting bacteria to enter E. coli cells was demonstrated using confocal microscopy. Since selected E. coli-specific RNA also affected the growth of this bacterium, we conclude that bacterial RNAs can participate in inter- and intraspecies signaling.

Synthesis of tridentate amine Pt(II) complexes and study of their reactions with purine and pyrimidine bases

1994 ◽  
Vol 72 (5) ◽  
pp. 1225-1229
Author(s):  
Fernande D. Rochon ◽  
Guylaine Laperrière
Keyword(s):  
The Other ◽  
New Method ◽  
Direct Reaction ◽  
Chloro Complexes ◽  
Methyl Group ◽  
Alkyl Groups ◽  
Nmr Techniques ◽  
Pyrimidine Bases ◽  
The One ◽  
Derivatives Of

Complexes of the type [Pt(L)X] where L is a tridentate N ligand and X = Cl or I, were synthesized and characterized. Three of the ligands are N-derivatives of diethylenetriamine, (2-aminoethyl)(N-dimethyl-2-aminoethyl)amine, (2-aminoethyl)(N-diethyl-2-aminoethyl)amine, and (2-aminoethyl)(N-methyl-2-aminoethyl)N-methylamine. The other two ligands are di(3-amino-propyl)amine and (2-aminoethyl)(3-aminopropyl)amine. A new method for the synthesis of the chloro complexes from the direct reaction of the amine with K2[PtCl4] was developed. The reactions of these five compounds with several purine and pyrimidine bases were studied by NMR techniques. The Pt(II) complexes containing two five-membered chelates were shown to be more reactive than the one containing two six-membered rings, while the complex containing one five- and one six-membered chelates showed intermediate reactivity. For the diethylenetriamine derivatives, the complexes containing ligands with two alkyl groups on the same terminal N atom were more reactive than the one containing one methyl group on a terminal N atom and one methyl group on a non-terminal N atom.

scholarly journals Synthesis and Characterization of New Compounds Derived from Pyrrolidine-2-One and Evaluation of their Biological Activities

2020 ◽  
Vol 23 (4) ◽  
pp. 5-12
Author(s):  
Nadia A. Betti ◽  
◽  
Redha Ib. Hussain ◽  
Sahar Ab. Kadhem ◽  
Abdul Jabar Kh. Atia ◽  
...  
Keyword(s):  
Biological Activity ◽  
Mass Spectrum ◽  
Biological Activities ◽  
The Other ◽  
Synthesis And Characterization ◽  
E Coli ◽  
Ft Ir ◽  
New Compounds ◽  
Derivatives Of

New derivatives of pyrrolidine-2-one have been prepared by lactamization of -butyrolactone GBL with hydrazine hydrate (NH2NH2(80%)) to afford (1-aminopyrrolidin-2-one) which undergo many reactions to prepare the other derivatives. The prepared derivatives were determined by utilizing their FT-IR,1H-NMR and some by Mass spectrum. These derivatives were evaluated biologically against (Staphylococcus aureusand E. coli).Some of these derivatives exhibited good biological activity against one or both kind of bacteria while some exhibited no biological activity at all.

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