Peptide inhibitors of N-succinyl diaminopimelic acid aminotransferase (DAP-AT): A novel class of antimicrobial compounds

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 8, 1998, Pages 945-950

  Cox, Russell J ^a   Schouten, James A ^a   Stentiford, Rosie A ^a   Wareing, Katrina J ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; BORANE DERIVATIVE; DIPEPTIDE; ENZYME INHIBITOR; HYDRAZINE DERIVATIVE; N SUCCINYL DIAMINOPIMELIC ACID AMINOTRANSFERASE; UNCLASSIFIED DRUG;

ANTIMICROBIAL ACTIVITY; ARTICLE; DRUG EFFICACY; DRUG POTENCY; ENZYME INHIBITION; ESCHERICHIA COLI; NONHUMAN;

ANTI-BACTERIAL AGENTS; DIPEPTIDES; ENZYME INHIBITORS; ESCHERICHIA COLI; GLUTAMATE DEHYDROGENASE; HYDRAZINES; INDICATORS AND REAGENTS; KINETICS; MOLECULAR STRUCTURE; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY; SUCCINYLDIAMINOPIMELATE TRANSAMINASE; TRANSAMINASES;

EID: 0032554693     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00149-8     Document Type: Article

References (17)

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10. 1H-nmr spectroscopy or HPLC analysis. All synthetic compounds gave satisfactory analytical data.
11. -1 with 1mM substrate 3 and 25μM NADPH.
12. 340/min, 0-20 mM substrate, 10 mM L-glutamate, 10 units of L-glutamate dehydrogenase (EC 1.4.1.4, Sigma) and Assay Solution to give a final volume of 1000 μL. Inhibition assays also contained inhibitor at concentrations of 1.0-50 μM. The decrease in β-NADPH concentration was observed at 340 nm over 300 seconds for activity assays and over 3600 seconds for inhibition testing. A Pharmacia-LKB Ultrospec III Spectrophotometer equipped with a cuvette having a heated-water jacket was used for all assays.
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16. 14 sterilised by autoclaving for 25 min at 120°C and poured into sterile 9 cm petri plates. E. coli DH5α was grown in liquid L media overnight at 37°C. The cells were precipitated and resuspended in M9 minimal liquid media. The washing process was repeated and 50 μl of the resulting cell suspension was evenly spread onto the surface of each sterile agar plate. Sterile filter disks (5mm diameter, whatman number 1 paper) were soaked with 3μl of a solution containing the appropriate amount of antibiotic dissolved in sterile deionised water. The filter disks were placed on the surface of the agar and the plates were incubated at 37°C for 16h (L-plates) or 36h (M9 minimal plates). The radius of the inhibition zone was measured and the radius of the filter disk (2.5mm) subtracted.
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