Differential effects of cyclopolyamines on the stability and conformation of triplex DNA

被引:4
作者
Antony, T
Musso, M
Hosseini, MW
Brand, G
Greenfield, NJ
Thomas, T
Van Dyke, MW
Thomas, TJ
机构
[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA
[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Community & Environm Med, New Brunswick, NJ 08903 USA
[3] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, New Brunswick, NJ 08903 USA
[4] Univ Texas, MD Anderson Cancer Ctr, Dept Tumor Biol, Houston, TX 77030 USA
[5] Univ Strasbourg 1, CNRS, Chim Coordinat Organ Lab, Inst Le Bel, F-67000 Strasbourg, France
来源
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT | 1999年 / 9卷 / 01期
关键词
D O I
10.1089/oli.1.1999.9.13
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Linear polyamines are excellent promoters of tripler DNA formation, The effects of structural rigidization of polyamines on tripler DNA stability are not known at present. We wished to develop a series of polyamine analogs as secondary ligands for tripler DNA stabilization for antigene applications, To accomplish this goal, we synthesized cyclopolyamines by interconnecting the two amino or imino groups of linear polyamines with a -(CH2)(n)-bridge (n = 3,4,5). Melting temperature (T-m) data showed that [4,3]-spermine and [4,4]-spermine stabilized poly(dA) . 2poly(dT) triplex at > 25 mu M concentrations (T-m = 71 degrees C at 100 mu M) The dTm/dlog [polyamine] values for these compounds were 26 and 40, respectively. [4,3]-Spermine and [4,4]-spermine also stabilized tripler DNA formed by a purine-motif tripler-forming oligonucleotide, TG(3)TG(4)TG(4)TG(3)T with its target duplex, as determined by T-m, circular dichroism (CD) spectroscopy, and electrophoretic mobility shift assay (EMSA), In contrast, [4,4]-putrescine and [4,5]-putrescine as well as [4,5]-spermine had no tripler DNA stabilizing effect. CD spectra also showed tripler DNA aggregation and Psi-DNA formation at > 100 mu M [4,3]-spermine, These data demonstrate that structural rigidization of linear polyamines has a profound effect on their ability to stabilize tripler DNA and provoke conformational transitions.
引用
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页码:13 / 23
页数:11
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