Premium
Effect of stereochemistry on ester hydrolysis by cholinesterases: Implications for radiotracer design
Author(s) -
Snyder Scott E.,
Shao Xia,
Lisi Jacinda M.,
Butch Elizabeth R.,
Skaddan Marc B.,
Kilboum Michael R.
Publication year - 2001
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580440138
Subject(s) - chemistry , medicine , library science , computer science
There is currently great interest in developing radiotracers to estimate cortical acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymatic activity in Alzheimer’s disease patients using in vivo imaging. As part of an ongoing effort to define structure-activity relationships (SAR) for cholinesterase substrates, we have recently published in vitro and in vivo kinetic results for a series of I-[”C]methyl-4-piperidinyl esters (1). These data exhibited the expected preference of AChE for short-chain esters (acetate and propionate) and the specificity of longerchain esters (butyrate and pentanoate) for BuChE. We have also shown that this general pattern of selectivity extends to the l-methylr3pyrrolidinyl esters, la,b (2). As these latter compounds are chiral, it was of interest to extend the SAR to include the effects of stereochemistry on enzyme selectivity and cleavage rates.