title: The impact of isomers of hemiaminal-1,2,4-triazole conjugates differently substituted in the phenyl ring and their Cu2+ complexes on the catalytic activity of the antigenomic delta ribozyme.
abstract: The ability of four stable hemiaminals differently substituted in the phenyl ring and their complexes with Cu(2+) ions to inhibit catalytic cleavage of the antigenomic delta ribozyme was compared. The hemiaminals were novel chiral derivatives of 1,2,4-triazole [i.e. (2,4-dinitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2,4-dnbald), (2-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (2-nbald), (3-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (3-nbald) and (4-nitrophenyl)(4H-1,2,4-triazol-4-ylamino) methanol (4-nbald)]. The complexes of nbalds with Cu(2+) were characterized using UV and EPR methods and additionally, the formation of 2,4-dnbald-Cu(2+) complex with CuL(2) stoichiometry was confirmed by mass spectrometry. The data suggest that there are two ways in which nbalds and their Cu(2+) complexes can influence catalytic cleavage of antigenomic delta ribozyme. The coordinated Cu(2+) ions may play the role of new cationic ligands increasing the affinity of the complexes to the ribozyme. Such situation occurs in the case of 2- and 2,4-nbald. Their Cu(2+) complexes decrease ribozyme cleavage rates twice more efficiently than uncomplexed compounds. Moreover, the Cu(2+) complexes displace the catalytic divalent metal ions from their strong binding sites located in the ribozyme J4/2 region as shown by the Pb(2+)-induced cleavage approach. On the other hand, 3- and 4-nbald inhibit catalysis more strongly as compared to 2-nbald and 2,4-dnbald but the ribozyme cleavage rates are changed only slightly upon Cu(2+) complexation. The mechanism of ribozyme inhibition by interfering with the formation of a correct ribozyme tertiary structure seems to operate in this case.
authors.affiliation: Faculty of Chemistry, University of Wrocław, Wrocław, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wrońska
authors.forename: Jan
authors.initials: J
authors.lastname: Wrzesinski
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jeżowska-Bojczuk
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szczepanik
authors.forename: Radosław
authors.initials: R
authors.lastname: Starosta
authors.forename: Maciej
authors.initials: M
authors.lastname: Barys
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Ciunik
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ciesiołka
mesh_terms: D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D008670:Metals; D016337:RNA, Catalytic; D014230:Triazoles; C045575:1,2,4-triazole; D003300:Copper