Verhandelingen - Koninklijke Academie voor Geneeskunde van België vol:57 issue:6 pages:601-615
Structure-based drug design is still a difficult achievable goal because many parameters describing non-covalent intermolecular interactions are known with insufficient accuracy. Here, we describe an example of a structural analysis of 5-substituted 2'-deoxyuridines and investigate if this analysis can be used to predict new molecules with antiviral activity. The target enzyme is the thymidine kinase of herpes simplex virus type. The physicochemical analysis of the 5-substituent demonstrate where substituents may be introduced and how the electrostatic potential isocontour maps have to look like, in order to obtain a compound with high affinity for the target enzyme. Taking into account these considerations, a new compound was synthesized which is recognized by substrate by the herpes simplex virus thymidine kinase. This demonstrates the predictability of the proposed theory.