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G-quadruplex formation of oligonucleotides containing ALS and FTD related GGGGCC repeat

Jasna Brčić,Janez Plavec

《化学科学与工程前沿（英文）》 2016年第10卷第2期页码 222-237 doi: 10.1007/s11705-016-1556-4

摘要： A largely increased number of GGGGCC repeats located in the non-coding region of gene have been identified as the leading cause of two related neurological disorders, familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We examined G-quadruplex forming ability of GGGGCC-repeat containing oligonucleotides with four guanine tracts chosen as the smallest possible model to form a unimolecular G-quadruplex. These oligonucleotides are readily to folded into G-quadruplexes in the presence of K ions. However, the formation of multiple structures makes structural analysis challenging and time consuming. We observed that flanking sequences on 5'- and 3'-ends as well as mutations of loop residues have a profound effect on folding. Sequence d[(G C ) G ] was chosen for further scrutiny and optimization of nuclear magnetic resonance (NMR) spectroscopic properties with dG to 8Br-dG substitutions at specific positions in the sequence under different folding conditions. Expectedly, folding into desired predominant topology is facilitated when substituted residue adopted a conformation in the naturally-occurring structure. Single dG to 8Br-dG substitution at position 21 and fine tuning of folding conditions facilitate folding of d[(G C ) GG GG] into (mostly) a single G-quadruplex, and thus enable determination of its high-resolution structure by high-field NMR.

关键词： G-quadruplex GGGGCC NMR ALS/FTD polymorphism

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微系统研究展望

钟先信

《中国工程科学》 2000年第2卷第1期页码 81-84

摘要：

微系统是在微米/纳米尺度上开展研究工作的，涉及到多种科学和技术领域，含微电子、微机械、微光学、化学、生物技术和材料等，它是多种技术的综合和多学科交叉的前沿领域，已显示出强大的生命力。微系统研究在传统理论和技术基础上起步和发展，人们在硅片上制作微型机械、微马达和光路系统微型化的惊喜之余，又引起了一些困惑和思考。人们必将冲破传统科学技术和思想，通过科研有所创新和突破，不断开拓进取，真正成为高新技术的生长点和面向市场新的经济增长点，开创21世纪新兴产业，这是当前迫切需要研究的课题。

现在，微系统研究的热点是：微域的科学和技术基础；新的信息获取、传输和处理技术；超精密检测和操作；微系统新材料和微制造技术。

关键词：微系统微域信息获取与处理纳米测量新材料微制造