DOUBLE-STRANDED CYCLIC OLIGONUCLEOTIDES WITH NON-NUCLEOTIDE BRIDGES

被引:30
作者
GAO, H [1 ]
CHIDAMBARAM, N [1 ]
CHEN, BC [1 ]
PELHAM, DE [1 ]
PATEL, R [1 ]
YANG, M [1 ]
ZHOU, L [1 ]
COOK, A [1 ]
COHEN, JS [1 ]
机构
[1] GEORGETOWN UNIV,MED CTR,CANC PHARMACOL SECT,WASHINGTON,DC 20007
关键词
D O I
10.1021/bc00029a011
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
A series of double-stranded, cyclic oligodeoxynucleotides with non-nucleotide bridges have been synthesized, and their physicochemical properties and susceptibility to enzymes have been investigated. These bridged duplexes are of potential interest for their binding properties to transcription factors and other DNA-binding proteins. Triethylene glycol has been employed as the bridge to alter the lipophilicity of the duplex and avoid the potential for enzymatic cleavage. The synthetic route involved the synthesis of a 3'-phosphorylated, nicked double-stranded precursor with the final internucleotide bond being formed chemically using a water soluble carbodiimide. These bridged duplexes have high thermal dissociation temperatures, and the T-m for a triethylene-bridged 20 base pair duplex was higher than that for the corresponding pentathymidylate-bridged duplex. EcoR I endonuclease cleaved a ligated, bridged duplex at a slower rate than the corresponding unmodified duplex, whereas the unligated, bridged duplex was cleaved more rapidly. Sufficient amounts of the bridged octamer and dodecamer were prepared for proton NMR spectroscopic studies, and 2D COSY and NOESY spectra were obtained. The results indicate that the ligated duplex has a B-form conformation.
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收藏
页码:445 / 453
页数:9
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