Growth Inhibition of
            <i>Escherichia coli</i>
            W by
            <scp>d</scp>
            -Norvalyl-
            <scp>d</scp>
            -Alanine: an Analogue of
            <scp>d</scp>
            -Alanine in Position 4 of the Peptide Subunit of Peptidoglycan

Neuhaus, Francis C.; Goyer, S.; Neuhaus, David

doi:10.1128/aac.11.4.638

Cited by 13 publications

(5 citation statements)

References 15 publications

(9 reference statements)

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“…DL-Propargylglycyl-L-alanine Trifluoroacetate (14). N-(tert-Butoxycarbonyl)-DL-propargylglycine (0.58 g, 2.7 mmol) was coupled to tert-butyl L-alaninate (0.50 g, 2.7 mmol) by the DCC coupling method described above for 11.…”

Section: Methodsmentioning

confidence: 99%

“…Among the antibacterials reported to be transported by a dipeptide permease is D-norvalyl-D-alanine, which inhibits the growth of E. coli K12, acts synergistically with D-cycloserine, and appears to replace DAla-nAla as a substrate in the synthesis of the UDP IV-acetylmuramyl pentapeptide. 3,14 The naturally occurring bacilysin, a dipeptide of L-alanine and L-anticapsin, is active against a wide range of bacteria and against the yeast Candida albicans. Anticapsin is a powerful inhibitor of glucosamine synthase isolated from both bacilysin-sensitive and -resistant strains of Staphylococcus aureus, but this amino acid alone has poor activity against whole bacterial cells.…”

Section: T H Imentioning

confidence: 99%

See 1 more Smart Citation

Chloroalanyl and propargylglycyl dipeptides. Suicide-substrate-containing antibacterials

Cheung¹,

Wasserman²,

Dudek³

et al. 1983

J. Med. Chem.

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A set of dipeptides containing the amino acid residues beta-chloroalanine and propargylglycine, which are mechanism-based inactivators of purified microbial enzymes (alanine racemase and cystathionine gamma-synthase, respectively), have been synthesized, and their antibacterial properties in vitro have been evaluated. Dipeptides containing a single beta-chloro-L-alanyl residue (e.g., 3, 5, 9, and 10) or a single L-propargylglycyl residue (e.g., 12 and 15) are potent antibacterials. The in vitro antibiotic activity of beta-chloro-L-alanine and of L-propargylglycine is increased as much as 4000-fold by incorporation of these residues into a dipeptide. Compounds that contain only a single enzyme-inactivating amino acid together with a second L-alanyl residue (3, 5, 12, and 15) have a restricted range of activity: of the species tested, only Streptococcus agalactiae, Staphylococcus aureus, and Staphylococcus epidermidis are sensitive. However, peptides that contain two suicide-substrate residues [e.g., beta-Cl-LAla-beta-Cl-LAla (8) or LppGly-LppGly (18)] are broad-spectrum antibacterials; as many as 12 different species of the 16 surveyed are sensitive. Dipeptides that contain an amino-terminal L-methionyl (9) or an L-norvalyl (10) residue and a carboxy-terminal beta-chloro-L-alanyl unit are also effective against a large number of organisms; the spectra of activity are like those seen for 8 and 18. A "mixed" dipeptide [beta-Cl-LAla-LppGly, (21)] gives apparent synergism of antibiotic action of beta-chloro-L-alanine and of L-propargylglycine when these two residues are incorporated into a single structure. Peptides of the D,D configuration (4, 6, 13, 16, and 20) and ones of L,D stereochemistry (e.g., 7) are not antibacterials. Peptides containing one (11 and 14) and two (17) D,L-propargylglycyl residues are unresolved sets of diastereomers; the mixtures of compounds are between two- and fourfold less active than the correspondingly resolved L,L dipeptides (12, 15, and 18). These findings are consistent with a mechanism of action for these antibiotics involving stereoselective processing of the peptidyl unit in vivo.

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Section: Methodsmentioning

confidence: 99%

Section: T H Imentioning

confidence: 99%

Chloroalanyl and propargylglycyl dipeptides. Suicide-substrate-containing antibacterials

Cheung¹,

Wasserman²,

Dudek³

et al. 1983

J. Med. Chem.

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show abstract

“…0006-2960/90/0429-2379502.50/0 © 1990 American Chemical Society to aid in the rational design of novel inhibitory compounds. Previous attempts at rational design of D-Ala-D-Ala analogues have yielded a number of compounds which show promising in vitro inhibitor activity but again are disappointing antibacterials in vivo (Smissman et al, 1976; Neuhaus et al, 1977; Pelzer & Reuter, 1980; Abo-Ghalia et al, 1988).…”

mentioning

confidence: 99%

Purification and characterization of the D-alanyl-D-alanine-adding enzyme from Escherichia coli

Duncan¹,

Heijenoort²,

Walsh³

1990

Biochemistry

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The Escherichia coli D-alanyl-D-alanine-adding enzyme, which catalyzes the final cytoplasmic step in the biosynthesis of the bacterial peptidoglycan precursor UDP-N-acetylmuramyl-L-Ala-gamma-D-Glu-meso-diaminopimelyl-D-Ala-D- Ala, has been purified to homogeneity from an E. coli strain that harbors a recombinant plasmid bearing the structural gene for this enzyme, murF. The enzyme is a monomer of molecular weight 49,000, and it has a turnover number of 784 min-1 for ATP-driven amide bond formation. Experiments monitoring the fate of radiolabeled UDP-N-acetylmuramyl-L-Ala-gamma-D-Glu-meso-2,6-diaminopimelate and D-trifluoroalanine proved that the preceding enzyme in the D-alanine branch pathway, D-alanine:D-alanine ligase (ADP), is capable of synthesizing fluorinated dipeptides, which the D-Ala-D-Ala-adding enzyme can then incorporate to form UDP-N-acetylmuramyl-L-Ala-gamma-D-Glu-meso-2,6-diaminopimelyl-D-++ +trifluoroAla-D- trifluoroAla.

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“…Earlier studies have shown that certain peptides, such as tri-L-ornithine (10), L-leucyl-glycine (30), D-norvalyl-D-alanine (21), and L-valyl-L-valyl-D-valine (25,26), had antimicrobial properties. Their activity seemed to depend on the action of the intact peptide on the microorganisms (20,24,28,29).…”

Section: Resultsmentioning

confidence: 99%

Phosphonopeptides as Antibacterial Agents: Rationale, Chemistry, and Structure-Activity Relationships

Atherton

Hali

Hassall

et al. 1979

Antimicrob Agents Chemother

108

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Peptide mimetics with C-terminal residues simulating natural amino acids have been designed as inhibitors of bacterial cell wall biosynthesis. The phosphonopeptide series consisting of various l and d residues of natural amino acids combined with 1-aminoalkyl (and aryl-alkyl-) phosphonic acid residues had the most interesting antibacterial properties when the C-terminal residue was l -1-aminoethylphosphonic acid. The in vitro antibacterial activities of representative phosphonodi- to phosphonohexapeptides were investigated. The antibacterial action of the active compounds has been explained in terms of transport into the bacterial cell and intracellular release of the alanine mimetic, which interferes with the biosynthesis of the peptidoglycan of the bacterial cell wall.

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Growth Inhibition of Escherichia coli W by d -Norvalyl- d -Alanine: an Analogue of d -Alanine in Position 4 of the Peptide Subunit of Peptidoglycan

Cited by 13 publications

References 15 publications

Chloroalanyl and propargylglycyl dipeptides. Suicide-substrate-containing antibacterials

Chloroalanyl and propargylglycyl dipeptides. Suicide-substrate-containing antibacterials

Purification and characterization of the D-alanyl-D-alanine-adding enzyme from Escherichia coli

Phosphonopeptides as Antibacterial Agents: Rationale, Chemistry, and Structure-Activity Relationships

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