PROPERTIES OF ARABINONUCLEIC ACIDS (ANA & 20′F-ANA): IMPLICATIONS FOR THE DESIGN OF ANTISENSE THERAPEUTICS THAT INVOKE RNASE H CLEAVAGE OF RNA

• Published in: Nucleosides, nucleotides & nucleic acids Vol. 20; no. 4-7; pp. 429 - 440
• Main Authors: Damha, M. J., Noronha, A. M., Wilds, C. J., Trempe, J.-F., Denisov, A., Pon, R. T., Gehring, K.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 01-04-2001
• Subjects: Arabinonucleotides - chemistry; Models, Molecular; Nucleic Acid Conformation; Ribonuclease H - chemistry; Ribonuclease H - metabolism; RNA - chemistry; RNA - metabolism; RNA, Antisense - chemistry; Stereoisomerism
• ISSN: 1525-7770; 1532-2335
• DOI: 10.1081/NCN-100002317

Inversion of configuration of the C2′ position of RNA leads to a very unique nucleic acid structure: arabinonucleic acid (ANA). ANA, and its 2′-fluoro derivative (2′ F-ANA) form hybrids with RNA that are capable of activating RNase H, resulting in cleavage of the RNA strand. In this paper, we review the properties of duplexes formed between ANA (or 2′F-ANA) and its RNA complement. These studies support the notion that RNase H is sensitive to the minor groove dimensions of the hybrid substrate.