Abstract
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.
ACKNOWLEDGMENT We wish to thank Professor K. Krnjević for his interest and encouragement throughout these studies.
- Copyright ©, 1971, by Academic Press, Inc.
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