A critical survey of the structure-function of the antisense oligo/RNA heteroduplex as substrate for RNase H.
The aim of this review is to draw a correlation between the structure of the DNA/RNA hybrid and its properties as a substrate for the RNase H, as well as to point the crucial structural requirements for the modified AONs to preserve their RNase H potency. The review is divided into the following parts: (1) mechanistic considerations, (2) target RNA folding-AON folding-RNase H assistance in AON/RNA hybrid formation, (3) carbohydrate modifications, (4) backbone modifications, (5) base modifications, (6) conjugated AONs, (7) importance of the tethered chromophore in AON for the AON/RNA hybrid interactions with the RNase H. The structural changes in the AON/RNA hybrid duplexes brought by different modifications of the sugar, backbone or base in the antisense strand, and the effect of these changes on the RNase H recognition of the modified substrates have been addressed. Only those AON modifications and the corresponding AON/RNA hybrids, which have been structurally characterized by spectroscopic means and functionally analyzed by their ability to elicit RNase H potency in comparison with the native counterpart have been presented here.
Zamaratski
E
E
Department of Bioorganic Chemistry, Box 581, Biomedical Center, University of Uppsala, S-75123, Uppsala, Sweden.
Pradeepkumar
P I
PI
Chattopadhyaya
J
J
D002241:Carbohydrates / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D016914:Ribonuclease H / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D002241:Carbohydrates; D009692:Nucleic Acid Heteroduplexes; D016376:Oligonucleotides, Antisense; D012313:RNA; D016914:Ribonuclease H