title: Synthesis of directly linked diazine isosteres of pyrrole-polyamide that photochemically cleave DNA.
abstract: A distamycin model containing an isosteric diazine linked pyrrole has been designed and synthesized. The key steps of the synthesis involved the successful diazotization of the 4-amino-pyrrole derivatives to give the diazomium salts, which undergo coupling reactions with N-methylpyrrole to yield the directly linked diazine compounds. The amide isosteric-diazine pyrrole I demonstrated photo-induced DNA damage upon iradiation with UV light (365 nm). Spectrophotometric and mass spectrometric identification suggest that the azo-linkage in I did not dissociate during irradiation. Moreover, compound I produced DNase I footprints with the HexB DNA fragment at AT sites, as well as some other mixed sequences (5'-ATGTCG-3'), indicative of the additional role of the diazine-linkage for interaction at the duplex DNA.
authors.affiliation: Department of Chemistry, National Sun Yat Sen University, No. 70, Lienhai Rd., Kaohsiung, 804, Taiwan, R.O.C. cong@mail.nsysu.edu.tw
authors.forename: Chi Wi
authors.initials: CW
authors.lastname: Ong
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Yang
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Liu
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fox
authors.forename: Ping Hao
authors.initials: PH
authors.lastname: Liu
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Tung
mesh_terms: D004247:DNA / Q000737:chemistry*; D003979:Diazonium Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D010782:Photolysis; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D003979:Diazonium Compounds; D004952:Esters; D009757:Nylons; D011758:Pyrroles; D004247:DNA