Conformational analysis of the reverse ester of acetylcholine, cholinergic potency, and cholinergic models

K. W. Reed, W. J. Murray, Edward B Roche, L. N. Domelsmith

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

1. 1. The conformational energy profile of the reverse ester of acetylcholine, a potent nicotinic agonist, was studied using EHT and PCILO molecular orbital calculations. 2. 2. The preferred conformation calculated by EHT has T1 = T2 = 180°, {A figure is presented} which is an extended molecule. 3. 3. The PCILO calculated preferred conformer has T1 = T2 = 60°, which corresponds to a folded molecule. 4. 4. The calculated preferred conformers do not match the preferred conformer given by X-ray crystallography. 5. 5. Comparison of the preferred conformations with the cholinergic potency of the reverse ester reveals that the models developed by Kier and by Chothia & Pauling for muscarinic and nicotinic activity cannot explain the activity of the reverse ester. 6. 6. A model based on the flexibility of the receptors and of the cholinergic molecules and electronic similarities in requisite atomic centers is necessary to explain the activity satisfactorily.

Original languageEnglish (US)
Pages (from-to)177-185
Number of pages9
JournalGeneral Pharmacology
Volume12
Issue number3
DOIs
StatePublished - Jan 1 1981

Fingerprint

Cholinergic Agents
Acetylcholine
Esters
Nicotinic Agonists
X Ray Crystallography
Cholinergic Receptors

ASJC Scopus subject areas

  • Pharmacology

Cite this

Conformational analysis of the reverse ester of acetylcholine, cholinergic potency, and cholinergic models. / Reed, K. W.; Murray, W. J.; Roche, Edward B; Domelsmith, L. N.

In: General Pharmacology, Vol. 12, No. 3, 01.01.1981, p. 177-185.

Research output: Contribution to journalArticle

Reed, K. W. ; Murray, W. J. ; Roche, Edward B ; Domelsmith, L. N. / Conformational analysis of the reverse ester of acetylcholine, cholinergic potency, and cholinergic models. In: General Pharmacology. 1981 ; Vol. 12, No. 3. pp. 177-185.
@article{cb3b58a016594b5589d124c5c70163e2,
title = "Conformational analysis of the reverse ester of acetylcholine, cholinergic potency, and cholinergic models",
abstract = "1. 1. The conformational energy profile of the reverse ester of acetylcholine, a potent nicotinic agonist, was studied using EHT and PCILO molecular orbital calculations. 2. 2. The preferred conformation calculated by EHT has T1 = T2 = 180°, {A figure is presented} which is an extended molecule. 3. 3. The PCILO calculated preferred conformer has T1 = T2 = 60°, which corresponds to a folded molecule. 4. 4. The calculated preferred conformers do not match the preferred conformer given by X-ray crystallography. 5. 5. Comparison of the preferred conformations with the cholinergic potency of the reverse ester reveals that the models developed by Kier and by Chothia & Pauling for muscarinic and nicotinic activity cannot explain the activity of the reverse ester. 6. 6. A model based on the flexibility of the receptors and of the cholinergic molecules and electronic similarities in requisite atomic centers is necessary to explain the activity satisfactorily.",
author = "Reed, {K. W.} and Murray, {W. J.} and Roche, {Edward B} and Domelsmith, {L. N.}",
year = "1981",
month = "1",
day = "1",
doi = "10.1016/0306-3623(81)90009-4",
language = "English (US)",
volume = "12",
pages = "177--185",
journal = "Vascular Pharmacology",
issn = "1537-1891",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Conformational analysis of the reverse ester of acetylcholine, cholinergic potency, and cholinergic models

AU - Reed, K. W.

AU - Murray, W. J.

AU - Roche, Edward B

AU - Domelsmith, L. N.

PY - 1981/1/1

Y1 - 1981/1/1

N2 - 1. 1. The conformational energy profile of the reverse ester of acetylcholine, a potent nicotinic agonist, was studied using EHT and PCILO molecular orbital calculations. 2. 2. The preferred conformation calculated by EHT has T1 = T2 = 180°, {A figure is presented} which is an extended molecule. 3. 3. The PCILO calculated preferred conformer has T1 = T2 = 60°, which corresponds to a folded molecule. 4. 4. The calculated preferred conformers do not match the preferred conformer given by X-ray crystallography. 5. 5. Comparison of the preferred conformations with the cholinergic potency of the reverse ester reveals that the models developed by Kier and by Chothia & Pauling for muscarinic and nicotinic activity cannot explain the activity of the reverse ester. 6. 6. A model based on the flexibility of the receptors and of the cholinergic molecules and electronic similarities in requisite atomic centers is necessary to explain the activity satisfactorily.

AB - 1. 1. The conformational energy profile of the reverse ester of acetylcholine, a potent nicotinic agonist, was studied using EHT and PCILO molecular orbital calculations. 2. 2. The preferred conformation calculated by EHT has T1 = T2 = 180°, {A figure is presented} which is an extended molecule. 3. 3. The PCILO calculated preferred conformer has T1 = T2 = 60°, which corresponds to a folded molecule. 4. 4. The calculated preferred conformers do not match the preferred conformer given by X-ray crystallography. 5. 5. Comparison of the preferred conformations with the cholinergic potency of the reverse ester reveals that the models developed by Kier and by Chothia & Pauling for muscarinic and nicotinic activity cannot explain the activity of the reverse ester. 6. 6. A model based on the flexibility of the receptors and of the cholinergic molecules and electronic similarities in requisite atomic centers is necessary to explain the activity satisfactorily.

UR - http://www.scopus.com/inward/record.url?scp=0019497559&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019497559&partnerID=8YFLogxK

U2 - 10.1016/0306-3623(81)90009-4

DO - 10.1016/0306-3623(81)90009-4

M3 - Article

VL - 12

SP - 177

EP - 185

JO - Vascular Pharmacology

JF - Vascular Pharmacology

SN - 1537-1891

IS - 3

ER -