Helix-Stabilizing Compounds CC-1065 and U-71,184 Bind to RNA-DNA and DNA-DNA Duplexes Containing Modified Internucleotide Linkages and Stabilize Duplexes Against Thermal Melting
作者:
DAE-YONG KIM,
DING S. SHIH,
D.-Y. CHO,
DAVID H. SWENSON,
期刊:
Antisense Research and Development
(MAL Available online 1995)
卷期:
Volume 5,
issue 1
页码: 49-57
ISSN:1050-5261
年代: 1995
DOI:10.1089/ard.1995.5.49
数据来源: MAL
摘要:
CC-1065 and U-71,184 bind and hyperstabilize DNA duplexes, but little is known about their effects on nucleic acid duplexes of different structure. A 20 mer DNA sequence (5′-TTACTTCAGTTATGAGACCA) containing a drug binding sequence (5′-AGTTA) was selected as the target sequence, and this was duplexed with complementary antisense sequences containing phosphodiester (PO), phosphorothioate (PS), and methylphosphonate (MP) bonds. The duplexes containing PO or PS bound 2 CC-1065 molecules per duplex, presumably at both the target site and at a lower affinity site (5′-AGTAA) on the antisense strand. The duplex containing MP bound only 1 CC-1065, and all duplexes bound only 1 U-71,184. Both CC-1065 and U-71,184 bound to 20 mer duplexes comprised of oligo(dA)-oligo(dT) (2.5 and 2 drugs per duplex, respectively) and poly(rA)-oligo(dT) (1 drug per 20 base pairs). CC-1065 also bound to duplexes between the PO- or PS-based antisense structures and a complementary synthetic 20 mer RNA sequence, with about 1 drug per duplex in each case. CC-1065 increased theTmfor the 20 mer DNA duplexes 17 to 29°C, and the corresponding values for U-71,184 ranged from 7 to 19°C. CC-1065 raised theTmof oligo(dA)-oligo(dT) and poly(rA)-oligo(dT) 29°C. U-71,184 increased theTmfor oligo(dA)-oligo(dT) 30°C but did not significantly elevate theTmfor the corresponding RNA-DNA duplex. The results show that CC-1065 and U-71,184 are capable of binding and stabilizing a variety of nucleic acid duplexes. These agents or their analogs may become useful ligands for antisense oligonucleotide app
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