Design of Phosphoramidite Monomer for Optimal Incorporation of Functional Intercalator to Main Chain of Oligonucleotide
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- 作者：Yun Shi ; Kenzo Machida ; Akinori Kuzuya ; and Makoto Komiyama
- 刊名：Bioconjugate Chemistry
- 出版年：2005
- 出版时间：March 2005
- 年：2005
- 卷：16
- 期：2
- 页码：306 - 311
- 全文大小：216K
- 年卷期：v.16,no.2(March 2005)
- ISSN：1520-4812
文摘
Chirally pure phosphoramidite monomers bearing 9-amino-6-chloro-2-methoxyacridine were synthesized from D- or L-threoninol and 
-aminocarboxylic acid, and incorporated into oligonucleotides. Theseacridine-DNA conjugates formed stable duplexes with complementary RNA because of intercalationof the acridine to DNA/RNA heteroduplexes. The stability of duplexes was not very dependent oneither the chirality of the central carbon bearing the acridine or the length of the side chain. However,the ability for site-selective activation of the phosphodiester linkage in front of the acridine, whichinduced Lu(III)-promoted RNA scission, was strongly dependent on these two factors. The largestactivation was achieved when the monomer unit was prepared from L-threoninol and 4-aminobutyricacid and the acridine was bound to the amino group. By attaching the more acidic 9-amino-2-methoxy-6-nitroacridine to this optimized scaffold, a quite effective acridine-DNA conjugate for site-selectiveRNA scission was obtained.
-aminocarboxylic acid, and incorporated into oligonucleotides. Theseacridine-DNA conjugates formed stable duplexes with complementary RNA because of intercalationof the acridine to DNA/RNA heteroduplexes. The stability of duplexes was not very dependent oneither the chirality of the central carbon bearing the acridine or the length of the side chain. However,the ability for site-selective activation of the phosphodiester linkage in front of the acridine, whichinduced Lu(III)-promoted RNA scission, was strongly dependent on these two factors. The largestactivation was achieved when the monomer unit was prepared from L-threoninol and 4-aminobutyricacid and the acridine was bound to the amino group. By attaching the more acidic 9-amino-2-methoxy-6-nitroacridine to this optimized scaffold, a quite effective acridine-DNA conjugate for site-selectiveRNA scission was obtained.