ISSN:
1574-6968
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Biologie
Notizen:
A series of mercaptophenylacetic acid thiol esters bearing a phenyl substituent adjacent to the carboxylic acid function has been shown to be inhibitors of metallo-β-lactamases. The inhibition of the Bacteroides fragilis CfiA and Bacillus cereus II metallo-β-lactamases was Zn2+ dependent, greater inhibition being observed at 1 μM ZnSO4 than at 100 μM ZnSO4. Despite this Zn2+ dependency, isothermal titration calorimetry studies illustrated that representative compounds had no detectable affinity for Zn2+ (K〉1 mM). This indicates that their mode of inhibition was not by chelation of the active site Zn2+. Greatest potency was observed against the Stenotrophomonas maltophilia L1 metallo-β-lactamase with I50 values of between 〈1.95 μM and 6 μM and SB-217843 exhibited a similar level of inhibition of this enzyme at 1 and 100 μM Zn2+ (I50 values 5 and 6 μM, respectively). Inhibition of B. cereus II metallo-β-lactamase by SB-218018 and SB-217782 was competitive with Ki values of 185 μM and 1500 μM, respectively. Therefore, these compounds are specific inhibitors of metallo-β-lactamases and provide further probes of the active sites of these enzymes.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1574-6968.1997.tb12769.x
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