The Development of Non-natural Type Nucleoside to Stabilize Triplex DNA Formation against CG and TA Inversion Site

Title:The Development of Non-natural Type Nucleoside to Stabilize Triplex DNA Formation against CG and TA Inversion Site

Volume: 31 Issue: 19

Author(s): Lei Wang*, Yong Ling, Yan Tian, Xiao Wang, Shigeki Sasaki and Yosuke Taniguchi*

Affiliation:

• School of Pharmacy, Nantong University, Nantong, China

• Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan

Keywords: Triplex-forming oligonucleotide (TFO), triplex DNA, inversion site, non-natural nucleotide, recognition, antigene strategy, deoxythymidine.

Abstract: Based on the sequence-specific recognition of target duplex DNA by triplexforming oligonucleotides (TFOs) at the major groove side, the antigene strategy has been exploited as a gene-targeting tool with considerable attention. Triplex DNA is formed via the specific base triplets by the Hoogsteen or reverse Hoogsteen hydrogen bond interaction between TFOs and the homo-purine strand from the target duplex DNA, leading to the established sequence-specificity. However, the presence of inversion sites, which are known as non-natural nucleosides that can form satisfactory interactions with 2′- deoxythymidine (dT) and 2′-deoxycytidine (dC) in TA and CG base pairs in the target homo-purine DNA sequences, drastically restricts the formation of classically stable base triplets and even the triplex DNA. Therefore, the design of non-natural type nucleosides, which can effectively recognize CG or/and TA inversion sites with satisfactory selectivity, should be of great significance to expanding the triplex-forming sequence. Here, this review mainly provides a comprehensive review of the current development of novel nonnatural nucleosides to recognize CG or/and TA inversion sites in triplex DNA formation against double-strand DNA (dsDNA).

Cite this article as:

Wang Lei*, Ling Yong, Tian Yan, Wang Xiao, Sasaki Shigeki and Taniguchi Yosuke*, The Development of Non-natural Type Nucleoside to Stabilize Triplex DNA Formation against CG and TA Inversion Site, Current Medicinal Chemistry 2024; 31 (19) . https://dx.doi.org/10.2174/0929867330666230512114130