Synthesis and antibacterial evaluation of phosphonic acid analogues of diaminopimelic acid

Assche, I. Van; Soroka, Mirosław; Haemers, Achiel; Hooper, M.; Blanot, Didier; Heijenoort, Jean van

doi:10.1016/0223-5234(91)90146-e

Cited by 34 publications

(16 citation statements)

References 31 publications

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“…35% for 5e and 5d). Here again, this was consistent with our previous result obtained with the mixture of the four stereoisomers (50% inhibition at 10 rnM) [14]. …”

Section: Fluorinated Analogue 8 [(2s3r6s)-3-fluoro-a2pmsupporting

confidence: 93%

“…This agreed with the result previously obtained with the unresolved mixture of the four isomers [14].…”

Section: Hooc~~~coohsupporting

confidence: 93%

“…This does not hold true for MurE, since monophosphonate compounds 5 are not substrates and are only weak inhibitors; moreover, the biphosphonate analogue (1,5-diaminopentane-l,5-diyl)diphosphonic acid (mixture of isomers) does not inhibit the enzyme at all [14]. Nevertheless, one can notice that, from a stereochemical point of view, the poorest inhibitor 5a corresponds to LL-A2pm (51t corresponding to Do-A2pm, and 5b and 5c to meso-A~pm): this may be another indication of the stricter stereochemical requirements of the distal recognition site.…”

Section: Discussionmentioning

confidence: 98%

“…There has been growing interest in the design and synthesis of A2pm analogues, some of which have been assayed either for antibacterial activity (see [3] for a recent example) or for a specific effect on the epimerase [4][5][6][7][8][9], the decarboxylase [9][10][11], the dehydrogenase [5,8,9] or less frequently the A2pm-adding enzyme [12][13][14][15]. Herein we take *Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

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Effect of analogues of diaminopimelic acid on the meso‐diaminopimelate‐adding enzyme from Escherichia coli

et al. 1996

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Several analogues of diaminopimelic acid (A2pm) were tested as substrates or inhibitors of the meso-diaminopimelate-adding enzyme from Escherichia coll. They included lanthionine derivatives, a phosphonic analogue, heterocyclic compounds, 3-fiuoro-A2pm, 4-methylene-A2pm and N-hydroxyA2pm. The best substrates were, in decreasing order of specific enzyme activity, (2S,3R,6S)-3-fluoro-A2pm, meso-lanthioulne sulfoxide and N-hydroxy-A2pm (mixture of stereoisomers). In those cases where all the stereoisomers were available, the specificity could be described as meso >> DD = LL. N-HydroxyA2pm (mixture of stereoisomers) strongly inhibited the addition of radioactive meso-A2pm to UDP-N-acetylmuramoyl-dipeptide.

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“…35% for 5e and 5d). Here again, this was consistent with our previous result obtained with the mixture of the four stereoisomers (50% inhibition at 10 rnM) [14]. …”

Section: Fluorinated Analogue 8 [(2s3r6s)-3-fluoro-a2pmsupporting

confidence: 93%

“…This agreed with the result previously obtained with the unresolved mixture of the four isomers [14].…”

Section: Hooc~~~coohsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Effect of analogues of diaminopimelic acid on the meso‐diaminopimelate‐adding enzyme from Escherichia coli

et al. 1996

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“…Analogues of A 2 pm (90% inhibition at 5 mM compound) and some N-acyl-dipeptide derivatives (IC 50 = 0.6-10 mM) have shown moderate inhibitory activities on MurE from Escherichia coli (Abo-Ghalia et al, 1985Michaud et al, 1990;van Assche et al, 1991;Le Roux et al, 1992;Auger et al, 1996). Phosphinates designed as transitionstate analogues of MurE inhibited the Escherichia coli enzyme in the micromolar range; the best of these (13) had an IC 50 value of 1.1 mM, whereas the derivative devoid of the UMP part was a poor inhibitor (IC 50 = 700 mM) (Zeng et al, 1998).…”

Section: Inhibitors Of the Mur Ligasesmentioning

confidence: 99%

Cytoplasmic steps of peptidoglycan biosynthesis

et al. 2008

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The biosynthesis of bacterial cell wall peptidoglycan is a complex process that involves enzyme reactions that take place in the cytoplasm (synthesis of the nucleotide precursors) and on the inner side (synthesis of lipid-linked intermediates) and outer side (polymerization reactions) of the cytoplasmic membrane. This review deals with the cytoplasmic steps of peptidoglycan biosynthesis, which can be divided into four sets of reactions that lead to the syntheses of (1) UDP-N-acetylglucosamine from fructose 6-phosphate, (2) UDP-N-acetylmuramic acid from UDP-N-acetylglucosamine, (3) UDP-N-acetylmuramyl-pentapeptide from UDP-N-acetylmuramic acid and (4) D-glutamic acid and dipeptide D-alanyl-D-alanine. Recent data concerning the different enzymes involved are presented. Moreover, special attention is given to (1) the chemical and enzymatic synthesis of the nucleotide precursor substrates that are not commercially available and (2) the search for specific inhibitors that could act as antibacterial compounds.

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Phosphinate Inhibitors of UDP‐N‐Acetylmuramoyl‐L‐Alanyl‐D‐Glutamate: L‐Lysine Ligase (MurE)

Štrancar

Boniface

Blanot

et al. 2007

Archiv der Pharmazie

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The increasing emergence of pathogenic bacterial strains with high resistance to antibiotic therapy has created an urgent need for the development of new antibacterial agents that are directed towards novel targets. We have focused our attention on the Mur ligases (MurC-F), which catalyze the early steps of bacterial peptidoglycan biosynthesis, and which to date represent under-exploited targets for antibacterial drug design. We show that some of our phosphinate inhibitors of UDP-N-acetylmuramoyl-L-alanyl:D-glutamate ligase (MurD) also inhibits UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine ligase (MurE). To obtain new information on their structure-activity relationships, three new, structurally related phosphinates were synthesized and evaluated for inhibition of MurD and MurE.

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Synthesis and antibacterial evaluation of phosphonic acid analogues of diaminopimelic acid

Cited by 34 publications

References 31 publications

Effect of analogues of diaminopimelic acid on the meso‐diaminopimelate‐adding enzyme from Escherichia coli

Effect of analogues of diaminopimelic acid on the meso‐diaminopimelate‐adding enzyme from Escherichia coli

Cytoplasmic steps of peptidoglycan biosynthesis

Phosphinate Inhibitors of UDP‐N‐Acetylmuramoyl‐L‐Alanyl‐D‐Glutamate: L‐Lysine Ligase (MurE)

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