1. A new automated micro-iodometric method is described for screening compounds for inhibitory action against β-lactamase enzymes. 2. Over 1000 semi-synthetic penicillins were tested for inhibitory activity against the β-lactamase of Escherichia coli B11 and 18 showed a fractional inhibition similar to or higher than that of methicillin. 3. The best inhibitors were alkoxy- and halogen-substituted phenyl-, naphthyl- or quinolyl-penicillins. 2-Isopropoxy-1-naphthylpenicillin (BRL 1437) was clearly the best and had a Ki value about 1% of that of methicillin. 4. The inhibition of the β-lactamase of E. coli B11 by BRL 1437 was shown to be reversible and competitive. The Ki was 0.004μm and Ki/Km with ampicillin and p-hydroxyampicillin (BRL 2333) was about 0.0001. The Km and Vmax. values were determined for the β-lactamases of E. coli B11 and Klebsiella aerogenes A against a variety of penicillins. Cell-bound and solubilized enzymes gave similar Ki and Km values. 5. BRL 1437 was superior to cloxacillin and methicillin for inhibition of the β-lactamase of live, fully grown cultures of several strains of E. coli and K. aerogenes. Of a group of inhibitors BRL 1437 was the most stable to the β-lactamase of E. coli B11.
Skip Nav Destination
Close
Article navigation
March 1972
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkAdvertising
Research Article|
March 01 1972
Inhibition of the β-lactamases of Escherichia coli and Klebsiella aerogenes by semi-synthetic penicillins
M. Cole;
M. Cole
1Beecham Research Laboratories, Brockham Park, Betchworth, Surrey, U.K.
Search for other works by this author on:
S. Elson;
S. Elson
1Beecham Research Laboratories, Brockham Park, Betchworth, Surrey, U.K.
Search for other works by this author on:
P. D. Fullbrook
P. D. Fullbrook
1Beecham Research Laboratories, Brockham Park, Betchworth, Surrey, U.K.
Search for other works by this author on:
Biochem J (1972) 127 (1): 295–308.
Citation
M. Cole, S. Elson, P. D. Fullbrook; Inhibition of the β-lactamases of Escherichia coli and Klebsiella aerogenes by semi-synthetic penicillins. Biochem J 1 March 1972; 127 (1): 295–308. doi: https://doi.org/10.1042/bj1270295
Download citation file:
Close
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Related Articles
Aging of di-isopropyl-phosphorylated human butyrylcholinesterase
Biochem J (October,1997)
Identification of some cleavage sites of insulin by insulin proteinase
Biochem J (December,1986)
β -Adrenoceptor Subtypes Mediating the Metabolic Effects of BRL 35135 in Man
Clin Sci (Lond) (March,1994)