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Binding of 2-(Triaz...
Binding of 2-(Triazolylthio)acetamides to Metallo-beta-lactamase CcrA Determined with NMR
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- Andersson, Hanna, Dr. 1979- (författare)
- Uppsala universitet,Organisk kemi
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- Jarvoll, Patrik, 1971 (författare)
- Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Centre for antibiotic resistance research, CARe,Univ Gothenburg, Ctr Antibiot Resistance Res CARe, SE-40530 Gothenburg, Sweden.
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- Yang, S. K. (författare)
- Northwest Univ, Coll Chem & Mat Sci, Key Lab Synthet & Nat Funct Mol Chem, Minist Educ, Xian 710127, Peoples R China.
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- Yang, K. W. (författare)
- Northwest Univ, Coll Chem & Mat Sci, Key Lab Synthet & Nat Funct Mol Chem, Minist Educ, Xian 710127, Peoples R China.
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- Erdelyi, Mate, 1975 (författare)
- Uppsala universitet,Gothenburg University,Göteborgs universitet,CARe - Centrum för antibiotikaresistensforskning,Centre for antibiotic resistance research, CARe,Organisk kemi
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(creator_code:org_t)
- 2020-08-18
- 2020
- Engelska.
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:34, s. 21570-21578
- Relaterad länk:
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https://pubs.acs.org...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Metallo-beta-lactamase (MBL)-producing bacteria resistant to beta-lactam antibiotics are a serious threat to human health. Despite great efforts and important progress in the discovery of MBL inhibitors (MBLIs), there is none in clinical use. Herein, inhibitor complexes of the MBL CcrA were investigated by NMR spectroscopy to provide perspectives on the further development of 2-(triazolylthio)acetamide-type MBLIs. By using the NMR-based chemical shift perturbation (CSP) and direction of CSP methodologies together with molecular docking, the spatial orientation of three compounds in the CcrA active site was investigated (4-6). Inhibitor 6 showed the best binding affinity (K-d approximate to 2.3 +/- 0.3 mu M), followed by 4 (K-d approximate to 11 +/- 11 mu M) and 5 (K-d = 34 +/- 43 mu M), as determined from the experimental NMR data. Based on the acquired knowledge, analogues of other MBLIs (1-3) were designed and evaluated in silico with the purpose of examining a strategy for promoting their interactions with the catalytic zinc ions.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- bacteroides-fragilis
- inhibitor discovery
- scaffold
- triazolylthioacetamide
- azolylthioacetamides
- Chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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