Covalent Schiff Base Catalysis and Turnover by a DNAzyme:  A M²⁺-Independent AP-Endonuclease Mimic

Abstract

A DNAzyme, synthetically modified with both primary amines and imidazoles, is found to act as a M2+ -independent AP lyase-endonuclease. In the course of the cleavage reaction, this DNAzyme forms a covalent Schiff base intermediate with an abasic site on a complementary oligodeoxyribonucleotide. This intermediate, which is inferred from NaCNBH3 trapping as well as cyanide inhibition, does not evidently accumulate because the second step, dehydrophosphorylative elimination, is fast compared to Schiff base formation. The 5'-product that remains linked to the catalyst hydrolyzes slowly to regenerate free catalyst. The use of duly modified DNAzymes to perform Schiff base catalysis demonstrates the value of modified nucleotides for enhancing the catalytic repertoire of nucleic acids. This work suggests that DNAzymes will be capable of catalyzing aldol condensation reactions.

Crystal structure of 2-bromo-4-chloro-6-[(4-chlorophenylimino) methyl]phenol, C13H8BrCl2NO

“…Schiff base ligands have played an important role in the development of coordination chemistry related to catalysis and enzymatic reactions [1,2], magnetism and molecular architectures [3,4] and biological properties [5,6]. 3-Bromo-5-chlorosalicylaldehyde is an important intermediate in synthesizing pesticides and drugs, andanactive aldehydeeasilytoreact with many amines, but the Schiff base with 4-chloroanilinehas notbeenreportedsofar.…”

2-{[4-(Diethylamino)phenyl]iminomethyl}-4,6-diiodophenol

“…For their role in biological processes, see: May et al (2004). For hydrogen-bond motifs, see: Bernstein et al (1995).…”

Synthesis and Structural Characterization of (2E,3E)-N1,N2-Bis(4-chlorobenzylidene)ethane-1,2-diamine

“…Schiff bases are known to have biological activities such as antimicrobial [2][3][4] , antitumor 5 and herbicidal properties 6 . They have also been widely used as versatile ligands involved in various metal chelation reactions to form metal complexes [7][8][9] , which are very intreresting in many fields, such as catalysis and enzymatic reactions 10,11 and magnetism 12 . Recently, a few Schiff base compounds with antibacterial activity have been investigated 4,[13][14][15] .…”