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

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• 作者：Magdalena Wroń ; ska^a ; Jan Wrzesinski^b ; ^{wrzesinj@ibch.poznan.pl} ; Mał ; gorzata Jeż ; owska-Bojczuk^a ; Wojciech Szczepanik^a ; Radosł ; aw Starosta^a ; Maciej Barys^a ; Zbigniew Ciunik^a ; Jerzy Ciesioł ; ka^b ; ^{ciesiolk@ibch.poznan.pl}
• 关键词：Delta ribozyme ; RNA catalysis ; Hemiaminals ; 1 ; 2 ; 4-triazole derivatives ; Metal ions
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2012
• 出版时间：March, 2012
• 年：2012
• 卷：108
• 期：Complete
• 页码：62-68
• 全文大小：559 K

文摘

The ability of four stable hemiaminals differently substituted in the phenyl ring and their complexes with Cu²⁺ 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 Cu²⁺ were characterized using UV and EPR methods and additionally, the formation of 2,4-dnbald-Cu²⁺ complex with CuL₂ stoichiometry was confirmed by mass spectrometry.

The data suggest that there are two ways in which nbalds and their Cu²⁺ complexes can influence catalytic cleavage of antigenomic delta ribozyme. The coordinated Cu²⁺ 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 Cu²⁺ complexes decrease ribozyme cleavage rates twice more efficiently than uncomplexed compounds. Moreover, the Cu²⁺ complexes displace the catalytic divalent metal ions from their strong binding sites located in the ribozyme J4/2 region as shown by the Pb²⁺-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 Cu²⁺ complexation. The mechanism of ribozyme inhibition by interfering with the formation of a correct ribozyme tertiary structure seems to operate in this case.