TMTFA

Last updated
TMTFA
TMTFA.png
Names
Preferred IUPAC name
N,N,N-Trimethyl-3-(trifluoroacetyl)anilinium
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C11H13F3NO/c1-15(2,3)9-6-4-5-8(7-9)10(16)11(12,13)14/h4-7H,1-3H3/q+1
    Key: JIBZSTPMDKSJOX-UHFFFAOYSA-N
  • C[N+](C)(C)C1=CC=CC(=C1)C(=O)C(F)(F)F
Properties
C11H13F3NO
Molar mass 232.226 g·mol−1
Hazards
Lethal dose or concentration (LD, LC):
1.6 mg/kg (intraperitoneal, mice) (as iodide salt) [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

TMTFA is an extremely potent acetylcholinesterase inhibitor. As a transition state analog of acetylcholinesterase, TMTFA is able to inhibit acetylcholinesterase at extremely low concentrations (within the femtomolar range), making it one of the most potent acetylcholinesterase inhibitors known. [2] [3] [4]

Contents

Mechanism of action

TMTFA has a reactive ketone group that can covalently bind to the serine residue in the active site of acetylcholinesterase. This is due to the electron-withdrawing trifluoromethyl group on the carbonyl group. [5]

See also

References

  1. ↑ Brodbeck, U.; Schweikert, K.; Gentinetta, R.; Rottenberg, M. (April 1979). "Fluorinated aldehydes and ketones acting as quasi-substrate inhibitors of acetylcholinesterase". Biochimica et Biophysica Acta (BBA) - Enzymology. 567 (2): 357–369. doi:10.1016/0005-2744(79)90122-0. PMID   444532.
  2. ↑ Nair, Haridasan K.; Lee, Keun; Quinn, Daniel M. (November 1993). "m-(N,N,N-Trimethylammonio)trifluoroacetophenone: a femtomolar inhibitor of acetylcholinesterase". Journal of the American Chemical Society. 115 (22): 9939–9941. Bibcode:1993JAChS.115.9939N. doi:10.1021/ja00075a009.
  3. ↑ Kua, Jeremy; Zhang, Yingkai; McCammon, J. Andrew (2002). "Studying Enzyme Binding Specificity in Acetylcholinesterase Using a Combined Molecular Dynamics and Multiple Docking Approach". Journal of the American Chemical Society. 124 (28): 8260–8267. Bibcode:2002JAChS.124.8260K. doi:10.1021/ja020429l. PMID   12105904.
  4. ↑ Butini, Stefania; Campiani, Giuseppe; Borriello, Marianna; Gemma, Sandra; Panico, Alessandro; Persico, Marco; Catalanotti, Bruno; Ros, Sindu; Brindisi, Margherita; Agnusdei, Marianna; Fiorini, Isabella; Nacci, Vito; Novellino, Ettore; Belinskaya, Tatyana; Saxena, Ashima; Fattorusso, Caterina (2008). "Exploiting Protein Fluctuations at the Active-Site Gorge of Human Cholinesterases: Further Optimization of the Design Strategy to Develop Extremely Potent Inhibitors". Journal of Medicinal Chemistry. 51 (11): 3154–3170. doi:10.1021/jm701253t. PMID   18479118.
  5. ↑ Harel, Michal; Quinn, Daniel M.; Nair, Haridasan K.; Silman, Israel; Sussman, Joel L. (January 1996). "The X-ray Structure of a Transition State Analog Complex Reveals the Molecular Origins of the Catalytic Power and Substrate Specificity of Acetylcholinesterase". Journal of the American Chemical Society. 118 (10): 2340–2346. Bibcode:1996JAChS.118.2340H. doi:10.1021/ja952232h.
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