About The Fast Lab
The Fast Lab is currently investigating the areas of infectious disease, cancer, and cardiovascular / pulmonary health. Researchers are guided by a broad curiosity about how enzymes work and how they can manipulate their functions. In most projects, the Fast Lab scientists studies the chemistry behind how these proteins accelerate chemical reactions that are important for biological processes. They use this information to develop small molecules to regulate the enzyme’s function, to design variant enzymes with altered functions or properties, or to design chemical probes to study the activity of enzymes within living cells. They choose to study enzymes that are suitable targets for new drugs, so their work also serves as an early step in the development of novel therapeutics.
2023 Research
- Dowsett L, Duluc L, Higgins E, Alghamdi F, Fast W, Salt IP, Leiper J. Asymmetric dimethylarginine positively modulates calcium-sensing receptor signalling to promote lipid accumulation. Cell Signal. 2023 Jul;107:110676. Epub 2023 Apr 5. PMID: 37028778.
2022 Research
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Price S, Mehta R, Tan D, Hinojosa A, Thomas PW, Cummings T, Fast W, Que EL. Structural insights into the design of reversible fluorescent probes for metallo-β-lactamases NDM-1, VIM-2, and IMP-1. J Inorg Biochem. 2022 Aug;233:111869. Epub 2022 May 20. PMID: 35653820; PMCID: PMC9216179.
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Johnson CM, Fast W. On the kinetic mechanism of dimethylarginine dimethylaminohydrolase. Bioorg Med Chem. 2022 Jul 15;66:116816. Epub 2022 May 13. PMID: 35598478.
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PW Thomas, EJ Cho, CR Bethel, T Smisek, YC Ahn, JM Schroeder, CA Thomas, KN Dalby, JT Beckham, MW Crowder, RA Bonomo, W Fast. Discovery of an Effective Small-Molecule Allosteric Inhibitor of New Delhi Metallo-β-lactamase (NDM). ACS Infect Dis. 2022 Apr 8;8(4):811-824. Epub. PMID: 35353502. March 30, 2022.
2021 Research
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CT Reidl, R Mascarenhas, TSH Mohammad, MR Lutz Jr, PW Thomas, W Fast, D Liu, DP Becker. Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-γ-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site. ACS Omega. 2021 May 17;6(21):13567-13578. eCollection. PMID: 34095651 Free PMC article. June 1, 2021.
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R Mehta, DD Rivera, DJ Reilley, D Tan, PW Thomas, A Hinojosa, AC Stewart, Z Cheng, CA Thomas, MW Crowder, AN Alexandrova, W Fast, EL Que. Visualizing the Dynamic Metalation State of New Delhi Metallo-β-lactamase-1 in Bacteria Using a Reversible Fluorescent Probe. J Am Chem Soc. 2021 Jun 9;143(22):8314-8323. Epub. PMID: 34038127. Free article. May 26, 2021.
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Z Cheng, CR Bethel, PW Thomas, BA Shurina, JP Alao, CA Thomas, K Yang, SH Marshall, H Zhang, AM Sturgill, AN Kravats, RC Page, W Fast, RA Bonomo, MW Crowder. Carbapenem Use Is Driving the Evolution of Imipenemase 1 Variants. Antimicrob Agents Chemother. 2021 Mar 18;65(4):e01714-20. PMID: 33468463 Free PMC article. March 18, 2021.
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YC Ahn, VK May, GC Bedford, AA Tuley, W Fast. Discovery of 4,4'-Dipyridylsulfide Analogs as "Switchable Electrophiles" for Covalent Inhibition. ACS Chem Biol. 2021 Feb 19;16(2):264-269. PMID: 33492128. February 19, 2021.
2020 Research
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MR Mehaffey, YC Ahn, DD Rivera, PW Thomas, Z Cheng, MW Crowder, RF Pratt, W Fast, Brodbelt Elusive structural changes of New Delhi metallo-β-lactamase revealed by ultraviolet photodissociation mass spectrometry. JS.Chem Sci. 2020 Aug 11;11(33):8999-9010. PMID: 34123154 Free PMC article. August 11, 2020.
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AY Chen, CA Thomas, PW Thomas, K Yang, Z Cheng, W Fast, MW Crowder, SM Cohen. Iminodiacetic Acid as a Novel Metal-Binding Pharmacophore for New Delhi Metallo-β-lactamase Inhibitor Development. ChemMedChem. 2020 Jul 20;15(14):1272-1282. PMID: 32315115 Free PMC article. July 20, 2021.
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Z Cheng, CA Thomas, AR Joyner, RL Kimble, AM Sturgill, NY Tran, MR Vulcan, SA Klinsky, DJ Orea, CR Platt, F Cao, B Li, Q Yang, CJ Yurkiewicz, W Fast, MW Crowder. MBLinhibitors.com, a Website Resource Offering Information and Expertise for the Continued Development of Metallo--Lactamase Inhibitors. Biomolecules. 2020 Mar 16;10(3):459. PMID: 32188106 Free PMC article. March 16, 2020.