Molecular Pharmacology, Vol 7, 33-39, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

The Use of Nuclear Magnetic Resonance to Describe the Binding of Atropine Analogues to Acetylcholinesterase

¹ Department of Research in Anaesthesia, McGill University, Montreal, Quebec, Canada

Proton magnetic resonance has been used to study the association of atropine and several of its analogues with acetylcholinesterase as indicated by changes in line width of the N-methyl and phenyl group resonances of the smaller molecule. Atropine and its analogues are bound to a site distinct from the active center of the enzyme. A direct involvement of the positively charged nitrogen and the phenyl group in the complex formation of atropine was established. Tropine and tropic acid bind very weakly, and a small alteration in the tropine moiety of atropine decreases its affinity for this site on the enzyme when compared with atropine. The l-form of atropine is more tightly bound than the d-isomer. The conclusions reached suggest a model for the site on the acetylcholinesterase molecule in which atropine bridges between a negative and a hydrophobic subsite.

Note:
ACKNOWLEDGMENT We wish to thank Professor K. Krnjevi for his interest and encouragement throughout these studies.