Article ; Online: Insertion of a methylene group into the backbone of an antisense oligonucleotide reveals the importance of deoxyribose recognition by RNase H.
Organic & biomolecular chemistry
2022 Volume 20, Issue 45, Page(s) 8917–8924
Abstract: RNase H acts as a key effector in gene knockdown by antisense oligonucleotides (ASOs). Although various chemical modifications have been developed to regulate RNase H-mediated cleavage, precise control is yet to be achieved. In this study, we tried to ... ...
| Abstract | RNase H acts as a key effector in gene knockdown by antisense oligonucleotides (ASOs). Although various chemical modifications have been developed to regulate RNase H-mediated cleavage, precise control is yet to be achieved. In this study, we tried to address the question of whether the interaction of phosphate groups or deoxyriboses is more important in the recognition of DNA/RNA duplex by RNase H. To answer this question, we investigated the effect of methylene group insertion at the 5'-upstream or 3'-downstream phosphorothioate groups on RNase H-mediated cleavage. By inserting a methylene group at the 5'-upside or 3'-downside, the distance between phosphates or deoxyriboses could be changed in a different pattern. Maximum suppression of the cleavage reaction was observed when a methylene group was inserted at the 5'-phosphate group of the nucleoside which is known to distinguish ribose and deoxyribose |
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| MeSH term(s) | Ribonuclease H/chemistry ; Oligonucleotides, Antisense/chemistry ; Deoxyribose ; Oligonucleotides/chemistry ; Phosphates |
| Chemical Substances | Ribonuclease H (EC 3.1.26.4) ; Oligonucleotides, Antisense ; Deoxyribose (533-67-5) ; Oligonucleotides ; Phosphates |
| Language | English |
| Publishing date | 2022-11-23 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2097583-1 |
| ISSN | 1477-0539 ; 1477-0520 |
| ISSN (online) | 1477-0539 |
| ISSN | 1477-0520 |
| DOI | 10.1039/d2ob01667b |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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