Change in the reactivity of the active‐site serine OH of butyrylcholinesterase caused by a new reversible inhibitor

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Abstract
The 2-chloro-12-(2-piperidinoethyl)-dibenzo[d,g] (1,3,6)-dioxazocine.cntdot.HCl (EGYT-2347), a new specific inhibitor of butyrylcholinesterase inhibits reversibly and non-competitively the enzymatic hydrolysis of butyrylthiocholine iodide (Ki [inhibition constant] = 0.15 .mu.M, at 37.degree. C in 0.1 M Tris/HCl, pH 7.5). The theoretical progress curve of product accumulation was developed for the case when a non-competitive reversible inhibitor (EGYT-2347) and an active-site-directed irreversible inhibitor (diisopropylfluorophosphate) act simultaneously. By the aid of this approach it was concluded that the butyrylcholinesterase-EGYT-2347 binary complex does not react with diisopropylfluorophosphate either because of a structural change caused by binding or by the direct steric hindrance of EGYT-2347.