title: Modelling of guanine-derivative--protein interaction complexes as a basis of drug design.
abstract: In rational drug design the study of protein-ligand-interactions is one of the most important approaches to get knowledge of SAR. On this study N2-Phenylthioguanines were synthesized by Schiemann reaction from thioguanine followed by a substitution of the fluorine by aniline-derivatives. The activity of these HSV1 TK inhibitors was determined by kinetic measurements of thymidine phosphorylation. The N2-Phenylthioguanines gave the same activity as the oxoanalogues. Interaction energies between thymidine and HSV1 TK were measured by microcalorimetry. Results of the measurement showed negative delta G and delta H values which indicates that the binding of the natural substrate occurs spontaneously and is enthalpy driven.
authors.affiliation: Department of Pharmacy, ETH Zürich.
authors.forename: G
authors.initials: G
authors.lastname: Folkers
authors.forename: A
authors.initials: A
authors.lastname: Prota
authors.forename: A
authors.initials: A
authors.lastname: Merz
mesh_terms: D002151:Calorimetry; D015195:Drug Design; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D011506:Proteins / Q000737:chemistry*; D018139:Simplexvirus / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors
chemical_list: D008024:Ligands; D011506:Proteins; D006147:Guanine; D013937:Thymidine Kinase