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R Engel

Publications and source records attributed to R Engel.

At least 91 records · Page 5Linked to original sources
PubMed1977

Synthesis of phosphonate and ether analogs of rac-phosphatidyl-L-serine.

The chemical synthesis of four phosphonate-containing phosphatidylserine analogs namely, L-serine (+/-)-[2,3-bis(hexadecyloxy) and 2,3-bis(Palmitoyloxy)-propyl] phosphonates, and L-serine (+/-)-[3,4-bis(hexadecyloxy and 3,4-bis(palmitoyloxy)-butyL]phosphonates is descirbed. (+/-)-2,3-Bis(hexadecyloxy) and 2,3-bis(palmitoyloxy)-prophylphosphonic acids and (+/-)-3,4-bis(hexadecyloxy)butylphosponic acid were prepared by reaction of tris(trimethylsily) phosphite on the corresponding haloalkane. Condensation of the above phosphonic acids or (+/-)-3,4-bis(palmitoyloxy)butylphosphonic acid with N-carboxy-L-serine dibenzyl ester in the presence of trichloroacetonitrile or triisopropylbenzenesulfonyl chloride yielded the protected serine intermediates, which on hydrogenolysis gave the desired L-serine analogs. By a similar route, 1,2-dihexadecyl-rac-glycero-3-phosphoric acid was converted to 1,2-dihexadecyl-rac-glycerophospho-L-serine (L-serine (+/-)-2,3-bis(hexadecyloxy)propyl hydrogen phosphate(ester).

Chromatography, Thin Layer↗
PubMed1977

Isosteres of natural phosphates. 5. The preparation of phosphotidycholine, phosphotidylethanolamine and phosphotidylglycerol.

Isosteric phosphonate analogues of phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol have been prepared in which the normal oxygen atom of the phosphate ester linkage in the glycerol backbone of the molecule has been replaced by a methylene group. These have been prepared by the coupling of the previously reported phosphotidic acid (isosteric analogue of phosphatidic acid) with the appropriate protected hydroxyl compound mediated by trichloroacetonitrile. In all cases, racemic materials have been isolated: for the analogue of phosphatidylglycerol, a mixture of two enantiomeric pairs is isolated.

Methods↗
PubMed1977

Isosteres of natural phosphates. 6. The preparation and properties of lysophosphotidic acid.

We herein report the first chemical synthesis of phosphonic acid analogues of lysophosphatidic acid. The racemic isosteric analogues, 4-acyloxy-3-hydroxybutyl-1-phosphonic acids, of lysophosphatidic acid were prepared by both catalytic and hydride reductions of the 4-acyloxy-3-oxobutyl-1-phosphonic acids, a general method for the preparation of the latter having been reported previously. The lysophosphatidic acids have been found to substrates for lysophosphatidic acid acyl transferase, and may be acylated chemically to yield phosphotidic acids. The latter reaction is of use in the preparations of differentially acylated phosphatidic acids.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1977

L-Glyceraldehude 3-phosphate, a bactericidal agent.

At a concentration of 2.5 mM, dl-glyceraldehyde 3-phosphate has a bactericidal effect upon Escherichia coli. The glycerol 3-phosphate transport system is required for the entry of the biologically active l-enantiomer. l-Glyceraldehyde must be phosphorylated by the cell to exert its full effect upon growth. The addition of dl-glyceraldehyde 3-phosphate to a culture of E. coli caused no preferential inhibition of the accumulation of deoxyribonucleic acid, ribonucleic acid, or phosphoglycerides, although protein accumulation was less affected. Studies with mutant strains ruled out catabolic glycerol 3-phosphate dehydrogenase, anabolic nicotinamide adenine dinucleotide (phosphate):sn-glycerol 3-phosphate oxidoreductase, and fructose 1,6-diphosphate aldolase as the primary sites of action. l-Glyceraldehyde 3-phosphate is a competitive inhibitor of sn-glycerol 3-phosphate in the reactions catalyzed by acyl coenzyme A:sn-glycerol 3-phosphate acyltransferase (K(i) of 1.8 mM) and cytidine 5'-diphosphate-diglyceride:sn-glycerol 3-phosphate phosphatidyltransferase (K(i) of 2.7 mM). A K(m) mutant for the former enzyme was susceptible to the inhibitor. l-Glyceraldehyde 3-phosphate does not affect acyl coenzyme A:lysophosphatidate acyltransferase activity. In vivo, phosphatidylethanolamine and phosphatidylglycerol accumulation are inhibited to the same extent by the addition of dl-glyceraldehyde 3-phosphate to a culture of E. coli.

Acyltransferases↗
PubMed1976

Metabolic fate of 3,4-dihydroxybutyl-1-phosphonate in Escherichia coli.

3,4-Dihydroxy[3-(3)H]butyl-1-phosphonate, and analogue of glycerol 3-phosphate, is incorporated into a very polar lipid material by cultures of Escherichia coli strain 8 and in vitro by CDP-diglyceride:sn-glycerol-3-phosphate phosphatidyltransferase. These labeled lipids have been fractionated by column chromatography on DEAE-cellulose, revealing that only one labeled compound is formed in vitro, while four are synthesized in vivo. The main component of the material formed by intact cells has been shown to be identical with that produced enzymatically. This species has been identified as the phosphonic acid analogue of phosphatidylglycerophosphate [(1,2-diacyl)-sn-glyceryl-D-4'-phosphoryloxy-3'-hydroxybutyl-1'-phosphonate]. Hydrolysis of this novel lipid with phospholipase C resulted in the production of diglyceride and a water-soluble derivative of 3,4-dihydroxybutyl-1-phosphonate and inorganic phosphate in a molar ratio of 1.03/1. Enzymatic analysis of the phosphonate liberated in this manner showed it to be the D enantiomer, thereby confirming the proposed structure of the lipid analogue. The analogue of phosphatidylglycerophosphate did not turn over and appeared to have no precursor-product relationship to the other labeled lipids derived from 3,4-dihydroxy[3-(3)H]butyl-1-phosphonate in vivo. Analysis of the other three labeled products revealed the tritium to be present on glycerol 3-phosphate and not intact phosphonate, indicating some metabolic degradation of the latter. Examination of cell components other than lipids revealed little incorporation of label, while a significant amount of tritium was found to be present in a distillable form, 3H2O. Experiments with mutants of E. coli lacking the known glycerol-3-phosphate dehydrogenases indicated that these enzymes are not responsible for the removal of tritium from from 3,4-dihydroxy[3-(3)H]butyl-1-phosphonate in vivo. Indirect evidence suggests that the inhibition of cell growth by this analogue is not due to its catabolic products.

Butylene Glycols↗
PubMed1976

Isosteres of natural phosphates. 4. The synthesis of phosphonic acid analogues of phosphatidic acid and acyldihydroxy acetone phosphate.

The chemical synthesis of 3,4-diacyloxybutyl-1-phosphonic acids having palmitoyl and oleoyl groups is described. These were prepared by reaction of the appropriate 3,4-diacyloxybutyl-1-bromide with tris(trimethylsilyl) phosphite followed by mild hydrolysis of the trimethyl-silyl groups from the phosphonic acid. Also reported is the preparation of 4-palmitoyl-3-oxobutyl-1-phosphonic acid by the acylation of 4-hydroxy-3-oxobutyl-1-phosphonic acid. This latter compound is an isosteric analogue of acyldihydroxyacetone phosphate.

Chromatography, Thin Layer↗
PubMed1976

[On the mechanism of action of acupuncture analgesia (author's transl)].

The correlation between the effects of acupuncture (A) and hypnosuggestion (H) on subjective pain perception was studied in normal volunteers using somatosensory evoked potentials technique. Both methods influenced identically the subjective pain perception and affected the evoked cortical responses similarly. In those subjects in whom analgesia was achieved, location of the A needles proved unimportant and the suppression of the cortical response elicited by A or H was identical. This could be explained by cortically induced inhibitory activity in descending control systems for both methods. A. analgesia thus appears to be a suggestive modality which depends on individual susceptibility. A specific cultural background also seems to be of importance.

Acupuncture Therapy↗
PubMed1975

Investigations concerning the mode of action of 3,4-dihydroxybutyl-1-phosphonate on Escherichia coli.

Experiments were performed to evaluate the ability of the enzymes of Escherichia coli involved in glycerol 3-phosphate metabolism to recognize phosphonic acid analogues of the natural substrate. Neither the catabolic membrane-bound glycerol-3-phosphate dehydrogenase nor the acyl coenzyme A: glycerol-3-phosphate acyltransferase can use 3,4-dihydroxybutyl-1-phosphnate or 2,3-dihydroxypropyl-1-phosphonate are inhibitors of the reduction of dihydroxyactone phosphate as substrates. The 4-carbon phosphonic acid analogue does not exhibit inhibitory activity for either of these enzymes. While the 3-carbon phosphonic acid analogue has no inhibitory effect upon the catabolic dehydrogenase, it does appear to have a slight but reproducible inhibitory effect on the acyltransferase. Glycerol 3-phosphate and 3,4-dihydroxybutyl-1-phosphonate by glycerol 3-phosphate:NAD (P) oxidoreductase. rac-2,3-Dihydroxypropyl-1-phosphonate does not appear to be recognized by this enzyme. The apparent K-i for snglycerol 3-phosphate is 19 muM and for D-3,4-dihydroxybutyl-1-phosphonate it is 42 muM. In addition the glycerol 3-phosphate:NAD(P) oxidoreductase catalyzes the reduction of 4-hydroxy-3-oxobutyl-1-phosphonate (apparent K-m of 182 muM), a phosphonic acid analogue of dihydroxyacetone phosphate. 3,4-Dihydroxybutyl-1-phosphonate is both a competitive inhibitor (apparent Ki of 740 muM) and a substrate (apparent K-m of 450 muM) for the CDP-diglyceride: glycerol 3 phosphate phosphatidyltransferase but it has no effect upon CDP-diglyceride:L-serine phosphatidyltransferase. The relationship ofthese in vitro studies to in vivo investigations is discussed.

Acyltransferases↗
PubMed1973

Effects of phosphonic acid analogues of glycerol-3-phosphate on the growth of Escherichia coli: phospholipid metabolism.

The effects of glycerol-3-phosphate, 3,4-dihydroxybutyl-1-phosphonate, and 2,3-dihydroxypropyl-1-phosphonate on the metabolism of Escherichia coli strains 8 and 1908 were determined. These strains lack the membrane-bound glycerol-3-phosphate dehydrogenase and are constitutive for the glycerol-3-phosphate transport system. Such cells were more sensitive to growth inhibition by the four-carbon phosphonate than by glycerol-3-phosphate. The three-carbon phosphonate did not appear to inhibit cell growth. The incorporation of labeled precursors of lipid, protein, ribonucleic acid, or deoxyribonucleic acid into bacterial cells was measured in the presence of either glycerol-3-phosphate or one of its phosphonic acid analogues. The phosphonic acid analogues inhibited the uptake of labeled acetate into the lipid fraction to the greatest extent. The incorporation of [(33)P]PO(4) into phospholipids was strongly inhibited by 3,4-dihydroxybutyl-1-phosphonate but was only slightly affected by 2,3-dihydroxypropyl-1-phosphonate. Glycerol-3-phosphate inhibited the incorporation of labeled uracil to the greatest extent during the first 20 min; however, this effect was largely reversed after 90 min. Only 3,4-dihydroxybutyl-1-phosphonate altered the distribution of labeled acetate into the phospholipids of strain 8, decreasing the percentage of counts in the phosphatidylglycerol fraction. The three-carbon phosphonate probably alters acetate incorporation by affecting the acetyl-coenzyme A pool, whereas the 3,4-dihydroxybutyl-1-phosphonate has a definite effect upon phospholipid metabolism. It is suggested that l-glycerol-3-phosphate:cytidine monophosphate phosphatidyltransferase is the probable site of action.

Escherichia coli↗