TMTFA

TMTFA
Names
Preferred IUPAC name
N,N,N-Trimethyl-3-(trifluoroacetyl)anilinium
Identifiers
3D model (JSmol)
ChemSpider
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)
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.

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.

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.