Site-Selective RNA Activation by Acridine-Modified Oligodeoxynucleotides in Metal-Ion Catalyzed Hydrolysis: A
Akinori Kuzuya1, Kenzo Machida2, Yun Shi2
1Department of Chemistry and Materials Engineering, Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan.
Abstract:
Various types of acridine were conjugated to DNA and used for site-selective RNA scission together with another unmodified DNA and a Lu(III) ion. The target phosphodiester linkage in the substrate RNA was selectively and efficiently activated, and was hydrolyzed by the free Lu(III) ion. Among the investigated 14 conjugates, the conjugate bearing 9-amino-2-isopropoxy-6-nitroacridine was the best RNA-activator. Systematic evaluation of the RNA-activating ability of the acridines showed that (1) the acridines act as an acid catalyst within the RNA activation, (2) the amino-group at the 9-position of acridine is essential to modulate the acidity of acridine, (3) the electron-withdrawing group at the 3-position further enhances the acid catalysis, and (4) the substituent at the 2-position sterically modulates the orientation of acridine-intercalation favorably for the catalysis. Moreover, it is revealed that the opposite base of acridine does not inhibit direct interaction of acridine with the target phosphodiester linkage.
Related Concept Videos
11:04Ion Mobility-Mass Spectrometry Techniques for Determining the Structure and Mechanisms of Metal Ion Recognition and Redox Activity of Metal Binding Oligopeptides
01:13Esters to Carboxylic Acids: Acid-Catalyzed Hydrolysis
During hydrolysis, the ester is first activated towards nucleophilic attack through the protonation of the carboxyl oxygen atom by the acid catalyst. The protonation makes the ester carbonyl carbon more electrophilic. In the next step, water acts as a nucleophile and adds to the...
01:15Hydrolysis
Hydrolysis is a chemical reaction in which the addition of water breaks down a polymer into its simpler monomer units. For example, peptides break into amino acids, carbohydrates into simple sugars, and DNA into nucleotides. Enzymes often facilitate these processes.
Hydrolysis Reverses Dehydration Synthesis
Complex carbohydrates can be broken down by breaking the bonds between individual sugar units. The reaction breaks a glycosidic bond as water is added to the compound. The...
01:08Hydrolysis of ATP
If one phosphate group is removed, a molecule of ADP—adenosine diphosphate—remains, along with inorganic phosphate. ADP can be further hydrolyzed to AMP—adenosine...
09:18Measurement of Extracellular Ion Fluxes Using the Ion-selective Self-referencing Microelectrode Technique
11:04Hydrolysis of an Ester