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Antimicrobial Agents and Chemotherapy, April 2007, p. 1577-1579, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01293-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Use of Novel Boronic Acid Transition State Inhibitors To Probe Substrate Affinity in SHV-Type Extended-Spectrum ß-Lactamases{triangledown}

Jodi M. Thomson,1 Fabio Prati,2 Christopher R. Bethel,3 and Robert A. Bonomo1,3*

Department of Pharmacology, Case Western Reserve University School of Medicine,1 Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio,3 Department of Chemistry, University of Modena, Modena, Italy2

Received 17 October 2006/ Returned for modification 20 November 2006/ Accepted 21 December 2006

Boronic acid transition state inhibitors (BATSIs) with R1 side chains of cefotaxime and ceftazidime were assayed against SHV-1, SHV-2, SHV-5, D104K, and D104K G238S ß-lactamases. The D104K variant was the most susceptible to inhibition by the ceftazidime BATSI (Ki, 730 ± 80 nM), while the D104K G238S variant was the most susceptible to the cefotaxime BATSI (Ki, 1.1 ± 0.2 µM).

* Corresponding author. Mailing address: Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, OH 44106. Phone: (216) 791-3800, ext. 4399. Fax: (216) 231-3482. E-mail: robert.bonomo{at}med.va.gov

{triangledown} Published ahead of print on 12 January 2007.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1577-1579, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01293-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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