Site-Specific Hydrolysis of RNA by Europium(III) Texaphyrin Conjugated to a Synthetic Oligodeoxyribonucleotide

• Published in: Journal of the American Chemical Society Vol. 116; no. 16; pp. 7439 - 7440
• Main Authors: Magda, D, Miller, R. A, Sessler, J. L, Iverson, B. L
• Format: Journal Article
• Language: English
• Published: American Chemical Society 01.08.1994
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja00095a070

There is considerable interest in the development of antisense agents that effect the hydrolysis of their RNA complement without the participation of endogenous nucleases. One of the more attractive ways of achieving this goal involves the use of metal complexes. For some time it has been known that certain lanthanide(III) metal cations and complexes catalyze the hydrolysis of RNA. Recently, we found this is also true for europium(III) chelated by the monoanionic, pentadentate texaphyrin ligand (EuTx, 1). In this communication we describe a DNA-EuTx conjugate based on the functionalized texaphyrin 2. To the best of our knowledge, this "ribozyme analogue" (cf., 3) provides the first example of an oligodeoxynucleotide-directed hydrolysis of a complementary RNA oligomer by a covalently attached metal complex. This communication thus links reports of metal cation-catalyzed hydrolysis of RNA to those of oligodeoxynucleotide-directed cleavage of DNA using oxidative and alkylation-based chemistry.