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Stability and bioactivity of thrombin binding aptamers modified with D-/L-isothymidine in the loop regions
Cai, Baobin; Yang, Xiantao; Sun, Lidan; Fan, Xinmeng; Li, Liyu; Jin, Hongwei; Wu, Yun; Guan, Zhu; Zhang, Liangren; Zhang, Lihe; Yang, Zhenjun
刊名ORGANIC & BIOMOLECULAR CHEMISTRY
2014
DOI10.1039/c4ob01525h
12期:44页:8866-8876
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Organic
研究领域[WOS]Chemistry
关键词[WOS]G-QUADRUPLEX ; DNA APTAMER ; BIOLOGICAL-PROPERTIES ; MOLECULAR-MECHANICS ; ACYCLIC NUCLEOTIDE ; SILENCING ACTIVITY ; CONTINUUM MODELS ; NUCLEIC-ACID ; OLIGONUCLEOTIDES ; D(GGTTGGTGTGGTTGG)
英文摘要

Thrombin binding aptamer (TBA) is a 15-mer single-strand DNA that was identified by SELEX screening technology. It adopts a chair-type antiparallel G-quadruplex and can specifically interact with thrombin, thus inhibiting blood coagulation. Isonucleoside (isoNA) is a type of nucleoside isomer in which the base is shifted to 2′-positions of the glycosyl group, endowed with the ability to modulate local conformation of nucleotides, and L-isoNA could alter the conformation more due to the inversion of glycosyl configuration. Incorporation of L-isothymidine (L-isoT) at T3, T9, T12 positions and D-isoT at the T7 position in TBA′s loop regions promoted the formation of G-quadruplex, resulting in enhanced affinity with thrombin and an increased anticoagulant effect. Computer simulation indicated that TBA-12L showed the strongest binding with thrombin, which was consistent with experimental results. The bioactivity of double isoNA incorporated TBA with D-IsoT at T7 and L-IsoT at T12 was comparable to that of TBA-12L, suggesting that the T12 of TBA was very important in interaction with thrombin. Our study also suggested that TBA might interact with two thrombin molecules through the TT loops (T3T4, T12T13) and TGT loop, but the second bonding did not show additional biological effects.

语种英语
WOS记录号WOS:000344236200011
项目编号2012CB720604 ; 2012AA022501 ; 21332010 ; 20932001
资助机构Ministry of Science and Technology of China ; National Natural Science Foundation of China
引用统计
被引频次:22[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62464
专题北京大学药学院
北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学药学院_药物化学系
北京大学第二临床医学院_消化科
作者单位Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Cai, Baobin,Yang, Xiantao,Sun, Lidan,et al. Stability and bioactivity of thrombin binding aptamers modified with D-/L-isothymidine in the loop regions[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2014,12(44):8866-8876.
APA Cai, Baobin.,Yang, Xiantao.,Sun, Lidan.,Fan, Xinmeng.,Li, Liyu.,...&Yang, Zhenjun.(2014).Stability and bioactivity of thrombin binding aptamers modified with D-/L-isothymidine in the loop regions.ORGANIC & BIOMOLECULAR CHEMISTRY,12(44),8866-8876.
MLA Cai, Baobin,et al."Stability and bioactivity of thrombin binding aptamers modified with D-/L-isothymidine in the loop regions".ORGANIC & BIOMOLECULAR CHEMISTRY 12.44(2014):8866-8876.
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