TMTFA is an extremely potent
acetylcholinesterase inhibitor
Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...
. As a
transition state analog
Transition state analogs (transition state analogues), are chemical compounds with a chemical structure that resembles the transition state of a substrate molecule in an enzyme-catalyzed chemical reaction. Enzymes interact with a substrate by mea ...
of
acetylcholinesterase
Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...
, TMTFA is able to inhibit acetylcholinesterase at extremely low concentrations (within the
femtomolar
Molar concentration (also called molarity, amount concentration or substance concentration) is the number of moles of solute per liter of solution. Specifically, It is a measure of the concentration of a chemical species, in particular, of a solu ...
range), making it one of the most potent acetylcholinesterase inhibitors known.
Mechanism of action
TMTFA has a reactive
ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
group that can covalently bind to the
serine
Serine
(symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...
residue in the active site of acetylcholinesterase. This is due to the electron-withdrawing
trifluoromethyl
The trifluoromethyl group is a functional group that has the formula . The naming of is group is derived from the methyl group (which has the formula ), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluoromethane ...
group on the
carbonyl
In organic chemistry, a carbonyl group is a functional group with the formula , composed of a carbon atom double bond, double-bonded to an oxygen atom, and it is divalent at the C atom. It is common to several classes of organic compounds (such a ...
group.
See also
*
Acetylcholinesterase inhibitor
Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...
*
Methylfluorophosphonylcholine
*
Transition state analog
Transition state analogs (transition state analogues), are chemical compounds with a chemical structure that resembles the transition state of a substrate molecule in an enzyme-catalyzed chemical reaction. Enzymes interact with a substrate by mea ...
References
{{Acetylcholine metabolism and transport modulators
Acetylcholinesterase inhibitors
Quaternary ammonium compounds
Aromatic ketones
Trifluoromethyl ketones
Acetophenones