title: Conformational analysis and receptor modelling of m1 and m2 selective antagonists.
abstract: On the basis of an elaborate conformational analysis of m1- and m2-selective antagonists a respective pharmacophore was deduced. This then was introduced into models of the two muscarinic receptor subtypes. These models were constructed starting from bacteriorhodopsin as a template in accordance with alignment data and mutation experiments. The validity of the interaction geometries between ligands and receptor subtypes is supported by a significant correlation between calculated interaction energies and experimentally determined affinity data.
authors.affiliation: Institut für Pharmazie der Freien Universität Berlin.
authors.forename: H
authors.initials: H
authors.lastname: Kerckhoff
authors.forename: H D
authors.initials: HD
authors.lastname: Höltje
mesh_terms: D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins / Q000737:chemistry; D003196:Computer Graphics; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000737:chemistry; D012984:Software
chemical_list: D008024:Ligands; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D001436:Bacteriorhodopsins