Novel synthetic analogs of the Pseudomonas autoinducer

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 24, 1999, Pages 3447-3452

  Kline, T ^a   Bowman, J ^a   Iglewski, B H ^b   De Kievit, T ^b   Kakai, Y ^b   Passador, L ^b  

^a NOVARTIS PHARMA AG   (Switzerland)

^b UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG ANALOG; LACTONE DERIVATIVE; TRANSCRIPTION FACTOR; VIRULENCE FACTOR;

AGONIST; ANIMAL CELL; ARTICLE; BACTERIUM MUTANT; DRUG SYNTHESIS; GENE EXPRESSION; GENE INDUCTION; NONHUMAN; PSEUDOMONAS AERUGINOSA; TRANSCRIPTION REGULATION;

PSEUDOMONAS; PSEUDOMONAS AERUGINOSA;

EID: 0033590261     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00626-5     Document Type: Article

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32. 660= 0.3 (approximately 2 h), 1 mL aliquots were added to tubes containing either various concentrations of the analogs being tested or control synthetic PAI-1. After allowing the cultures to grow for 1 h, β-galactosidase activity was measured. For the antagonist assay, 1 mL aliquots of an overnight culture of a PAO-JP2(lasI-lacZ) culture, described above, were added to tubes containing either the analogs being tested (at a concentration of 1 μM) or control synthetic PAI-1 (40 nM - previously determined to be the concentration required for half-maximal activation of lasI-lacZ). The cultures were then allowed to grow for 15 min. After this time, 1 mL aliquots of each culture were added to 2 tubes: the first tube contained no PAI-1; the second tube contained 40 nM PAI-1. The cultures were allowed to grow for an additional hour before being assayed for β-galactosidase activity. The PAI-2 agonist and antagonist assays were essentially the same as that described for PAI-1 except that PDO-100(rhlA-lacZ) was used as the reporter strain. Furthermore, in the PAI-2 antagonist assay 10 μM PAI-2 was added to the tubes after the fifteen minute incubation with test analog. This concentration was used to maximize the assay sensitivity, and the PAI-2 assays are less sensitive than those of PAI-1.
33. 3H]-PAI-1 (125 Ci/mmol) and returned to the 25 °C incubation for an additional 15 min. Following the second incubation, the tubes were spun at 16,000 x g for 10 min and the pellets resuspended in cold phosphate buffered saline (PBS, pH 7.2). The cells were pelleted twice more and the final pellet was resuspended in 30-50 μL of PBS. The resuspended pellets were placed into a scintillation vial containing scintillation fluid (Ecoscint A) and counted.