Journal
CHEMICAL COMMUNICATIONS
Volume 52, Issue 40, Pages 6727-6730Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c6cc00529b
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Funding
- Medical Research Council (MRC) [MR/L007665/1]
- Agency for Science, Technology and Research Singapore (A<SUP>star</SUP>STAR)
- AbbVie [1097737]
- Bayer Pharma AG
- Boehringer Ingelheim
- Canada Foundation for Innovation
- Genome Canada
- Janssen
- Merck Co.
- Novartis Research Foundation
- Ontario Ministry of Economic Development and Innovation
- Pfizer
- Sao Paulo Research Foundation-FAPESP
- Takeda
- Wellcome Trust [092809/Z/10/Z]
- MRC [MR/L007665/1] Funding Source: UKRI
- Cancer Research UK [16466] Funding Source: researchfish
- Medical Research Council [MR/L007665/1] Funding Source: researchfish
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Bacterial metallo-beta-lactamases (MBLs) are involved in resistance to beta-lactam antibiotics including cephalosporins. Human SNM1A and SNM1B are MBL superfamily exonucleases that play a key role in the repair of DNA interstrand cross-links, which are induced by antitumour chemotherapeutics, and are therefore targets for cancer chemosensitization. We report that cephalosporins are competitive inhibitors of SNM1A and SNM1B exonuclease activity; both the intact b-lactam and their hydrolysed products are active. This discovery provides a lead for the development of potent and selective SNM1A and SNM1B inhibitors.
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