Abstract
A conformational study for a pyridinium analogue of acetylcholine has been performed by a semiempirical approach using the PCILO method. The results have been compared with those of previous PCILO studies on cholinergic molecules. Our analysis shows that the N-(β-acetoxyethyl)pyridinium ion (PyACh) has an absolute minimum for a gauche-gauche conformation. The gauche conformation characteristic of acetylcholine (ACh) remains a local minimum. The more crowded conformation of PyACh is related to intramolecular interactions between the anionic and cationic heads, which are more effective than in ACh due to the reduced spherical screening around the nitrogen atom. This characteristic and the consequently low conformational flexibility of PyACh could explain the reduced biological activity of pyridinium analogues of ACh.
ACKNOWLEDGMENTS The authors wish to thank Prof. G. Martino for helpful discussions, Miss L. Pastore and Miss G. Del Prete for technical assistance, and the Computer Center at the University of Calabria for the generous gift of computer time.
- Copyright © 1980 by The American Society for Pharmacology and Experimental Therapeutics
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