title: Toward efficient Zn(II)-based artificial nucleases.
abstract: A series of cis-cis-triaminocyclohexane Zn(II) complex-anthraquinone intercalator conjugates, designed in such a way to allow their easy synthesis and modification, have been investigated as hydrolytic cleaving agents for plasmid DNA. The ligand structure comprises a triaminocyclohexane platform linked by means of alkyl spacers of different length (from C(4) to C(8)) to the anthraquinone group which may intercalate the DNA. At a concentration of 5 microM, the complex of the derivative with a C(8) alkyl spacer induces the hydrolytic stand scission of supercoiled DNA with a rate of 4.6 x 10(-6) s(-1) at pH 7 and 37 degrees C. The conjugation of the metal complex with the anthraquinone group leads to a 15-fold increase of the cleavage efficiency when compared with the anthraquinone lacking Zn-triaminocyclohexane complex. The straightforward synthetic procedure employed, allowing a systematic change of the spacer length, made possible to gain more insight on the role of the intercalating group in determining the reactivity of the systems. Comparison of the reactivity of the different complexes shows a remarkable increase of the DNA cleaving efficiency with the length of the spacer. In the case of too-short spacers, the advantages due to the increased DNA affinity are canceled due to the incorrect positioning of the reactive group, thus leading to cleavage inhibition.
authors.affiliation: Dipartimento di Scienze Chimiche e Istituto CNR Tecnologia delle Membrane-Sezione di Padova, Università di Padova, via Marzolo 1, I-35131 Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Boseggia
authors.forename: Maddalena
authors.initials: M
authors.lastname: Gatos
authors.forename: Lorena
authors.initials: L
authors.lastname: Lucatello
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mancin
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Manlio
authors.initials: M
authors.lastname: Palumbo
authors.forename: Claudia
authors.initials: C
authors.lastname: Sissi
authors.forename: Paolo
authors.initials: P
authors.lastname: Tecilla
authors.forename: Umberto
authors.initials: U
authors.lastname: Tonellato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zagotto
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003851:Deoxyribonucleases / Q000737:chemistry* / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000880:Anthraquinones; D003510:Cyclohexanes; D007364:Intercalating Agents; D009942:Organometallic Compounds; D003851:Deoxyribonucleases; D015032:Zinc