title: Computer-aided molecular modeling and design of DNA-inserting molecules.
abstract: Intercalators are molecules capable of sliding between base pairs without disturbing the overall stacking pattern. In addition, there may exist molecules capable of inserting into a base pair thereby disrupting the hydrogen bonds and replacing them with new hydrogen bonds. A molecule probably capable of inserting, i.e., an insertor, is the diketopiperazine cyclo-[Gly-Gly] (1). A barbiturate (2), alloxan (3), a pyrimidine derivative (4) and a hydantoin (5) were also studied as possible insertors. Furthermore, molecules such as ethyleneurea (6), succinimide (7), as well as a malonamide derivative (8) and oxamide derivatives (9-11) were studied in order to investigate the arrangement and the number of hydrogen bonds necessary for insertion. Molecules 12-14 were designed and studied for their capacity to act as bisinsertors and/or bisintercalators. These molecules feature two diketopiperazine moieties which are connected via a diphenyl(thio)ether, i.e., 12 and 13, or a bisphenol A spacer, i.e., 14. The latter molecule (14) seems a promising candidate as a bisinsertor.
authors.affiliation: Department of Chemistry, Gorlaeus Laboratories, University of Leiden, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: van der Klein-de Gunst
authors.forename: J H
authors.initials: JH
authors.lastname: van Boom
authors.forename: R M
authors.initials: RM
authors.lastname: Liskamp
mesh_terms: D003201:Computers; D004247:DNA / Q000737:chemistry; D015195:Drug Design; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D007364:Intercalating Agents; D004247:DNA