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Title: Theoretical studies of the activation mechanism of histamine H sub 2 -receptors: Dimaprit and the receptor model

Abstract

Ab initio quantum mechanical calculations are used to explore the interaction of dimaprit, a histamine H,-receptor agonist, with a molecular complex designed to model the specific recognition of histamine, and the H{sub 2}-receptor activation mechanism triggered by the binding of the ligand. The stabilization of several isomeric forms of the isothiourea moiety of dimaprit in the receptor model is considered, including models for the monocationic and dicationic forms that are likely to exist under physiological conditions. The energetics of proton transfer from a receptor site to the ligand are evaluated in the presence and absence of models for other sites in the receptor. The energetic contribution of ligand desolvation to the various steps in the receptor binding and activation mechanism is estimated from calculations of the enthalpy of solvation in water represented as a continuum dielectric. The results indicate that the most likely manner in which dimaprit mimics the binding of histamine to the proposed proton donor site in the H{sub 2}-receptor model requires the sulfur in the isothiourea moiety of dimaprit to act as the proton acceptor in the activation mechanism. The simulation of this mechanism reveals its feasibility and indicates that the monocation form of dimaprit, rather thanmore » the dication, is likely to be the physiologically active species.« less

Authors:
; ; ;  [1]
  1. City Univ. of New York,NY (USA)
Publication Date:
OSTI Identifier:
6415737
Report Number(s):
CONF-8904365-
Journal ID: ISSN 0020-7608; CODEN: IJQCB
Resource Type:
Conference
Journal Name:
International Journal of Quantum Chemistry; (USA)
Additional Journal Information:
Journal Volume: 16; Conference: International symposium on quantum biology and quantum pharmacology, St. Augustine, FL (USA), 1-8 Apr 1989; Journal ID: ISSN 0020-7608
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; HISTAMINE; RECEPTORS; STRUCTURE-ACTIVITY RELATIONSHIPS; LIGANDS; MATHEMATICAL MODELS; PROTONS; AMINES; AZOLES; BARYONS; ELEMENTARY PARTICLES; FERMIONS; HADRONS; HETEROCYCLIC COMPOUNDS; IMIDAZOLES; MEMBRANE PROTEINS; NUCLEONS; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PROTEINS; 550200* - Biochemistry

Citation Formats

Pardo, L, Mazurek, A P, Osman, R, and Weinstein, H. Theoretical studies of the activation mechanism of histamine H sub 2 -receptors: Dimaprit and the receptor model. United States: N. p., 1989. Web.
Pardo, L, Mazurek, A P, Osman, R, & Weinstein, H. Theoretical studies of the activation mechanism of histamine H sub 2 -receptors: Dimaprit and the receptor model. United States.
Pardo, L, Mazurek, A P, Osman, R, and Weinstein, H. 1989. "Theoretical studies of the activation mechanism of histamine H sub 2 -receptors: Dimaprit and the receptor model". United States.
@article{osti_6415737,
title = {Theoretical studies of the activation mechanism of histamine H sub 2 -receptors: Dimaprit and the receptor model},
author = {Pardo, L and Mazurek, A P and Osman, R and Weinstein, H},
abstractNote = {Ab initio quantum mechanical calculations are used to explore the interaction of dimaprit, a histamine H,-receptor agonist, with a molecular complex designed to model the specific recognition of histamine, and the H{sub 2}-receptor activation mechanism triggered by the binding of the ligand. The stabilization of several isomeric forms of the isothiourea moiety of dimaprit in the receptor model is considered, including models for the monocationic and dicationic forms that are likely to exist under physiological conditions. The energetics of proton transfer from a receptor site to the ligand are evaluated in the presence and absence of models for other sites in the receptor. The energetic contribution of ligand desolvation to the various steps in the receptor binding and activation mechanism is estimated from calculations of the enthalpy of solvation in water represented as a continuum dielectric. The results indicate that the most likely manner in which dimaprit mimics the binding of histamine to the proposed proton donor site in the H{sub 2}-receptor model requires the sulfur in the isothiourea moiety of dimaprit to act as the proton acceptor in the activation mechanism. The simulation of this mechanism reveals its feasibility and indicates that the monocation form of dimaprit, rather than the dication, is likely to be the physiologically active species.},
doi = {},
url = {https://www.osti.gov/biblio/6415737}, journal = {International Journal of Quantum Chemistry; (USA)},
issn = {0020-7608},
number = ,
volume = 16,
place = {United States},
year = {Sun Jan 01 00:00:00 EST 1989},
month = {Sun Jan 01 00:00:00 EST 1989}
}

Conference:
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