Zhang Xiaohua, Bruice Thomas C
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
Bioorg Med Chem Lett. 2008 Jan 15;18(2):665-9. doi: 10.1016/j.bmcl.2007.11.061. Epub 2007 Nov 21.
Cancerous cell immortality is due to relatively high concentrations of telomerase enzyme which maintains telomere sequence during cell division. Deoxyribonucleic guanidine (DNG) is a positively charged DNA analog in which guanidine replaces the phosphordiester linkage of DNA. Mixed sequences of DNG and DNA oligonucleotides are referred to as chimera. Complexation of DNG and chimeric polycations with the complementary negatively charged non-coding telomere single strand d(5'-TTAGGG-3')(n) and the 11-base telomeric RNA template (5'-CUAACCCUAAC-3') in the active site of telomerase has been studied. Calculated by ensemble sampling simulations in GBMV solvent model, we found that binding of complementary DNG hexamer with telomere is favored over that of DNA-telomere by approximately 10(6)-fold and binding of chimera hexamer is favored by approximately 10(4)-fold. Binding of complementary DNG with telomeric RNA is favored by 43 kcal/mol over telomere substrate binding with telomeric RNA.
癌细胞的永生归因于相对高浓度的端粒酶，该酶在细胞分裂过程中维持端粒序列。脱氧核糖核酸胍（DNG）是一种带正电荷的DNA类似物，其中胍取代了DNA的磷酸二酯键。DNG和DNA寡核苷酸的混合序列被称为嵌合体。已经研究了DNG和嵌合聚阳离子与端粒酶活性位点中带负电荷的互补非编码端粒单链d(5'-TTAGGG-3')(n)和11碱基端粒RNA模板（5'-CUAACCCUAAC-3'）的复合作用。通过在GBMV溶剂模型中的系综抽样模拟计算，我们发现互补DNG六聚体与端粒的结合比DNA-端粒的结合大约有利10^6倍，嵌合六聚体的结合大约有利10^4倍。互补DNG与端粒RNA的结合比端粒底物与端粒RNA的结合有利43千卡/摩尔。
