title: Molecular design using the minireceptor concept.
abstract: Explicit molecular binding pockets were constructed and optimized around sets of superimposed ligands using the minireceptor concept. The resulting binding sites incorporate the properties of the different ligands and were shown to be suitable for the design of molecules presenting novel interaction patterns. Two applications of minireceptor construction and/or optimization, followed by molecular design are described. In the pursuit of new ligands mimicking the action of paclitaxel, a minireceptor was constructed using the primary amino acid sequence of the target protein as a guide. The active site extracted from a homology-based model of the serotonin 5-HT1A receptor was optimized around a set of three ligands using the same approach.
authors.affiliation: Department of Organic Pharmaceutical Chemistry, Uppsala University, Sweden. Johanna.Jansen@draco.se.astra.com
authors.forename: J M
authors.initials: JM
authors.lastname: Jansen
authors.forename: K F
authors.initials: KF
authors.lastname: Koehler
authors.forename: M H
authors.initials: MH
authors.lastname: Hedberg
authors.forename: A M
authors.initials: AM
authors.lastname: Johansson
authors.forename: U
authors.initials: U
authors.lastname: Hacksell
authors.forename: G
authors.initials: G
authors.lastname: Nordvall
authors.forename: J P
authors.initials: JP
authors.lastname: Snyder
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008024:Ligands; D011956:Receptors, Cell Surface; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017239:Paclitaxel