Sensitive CEST agents based on nucleic acid imino proton exchange:: Detection of poly(rU) and of a dendrimer-poly(rU) model for nucleic acid delivery and pharmacology

Sensitive CEST agents based on nucleic acid imino proton exchange:: Detection of poly(rU) and of a dendrimer-poly(rU) model for nucleic acid delivery and pharmacology
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DOI:
10.1002/mrm.10463
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发表时间:
2003-06-01
影响因子:
3.3
通讯作者:
van Zijl, PCM
van Zijl, PCM
中科院分区:
医学3区
文献类型:
--
作者:
Snoussi, K;Bulte, JWM;van Zijl, PCM

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结果表明,多尿酸(poly(ru))的伊米诺和羟基质子的交换特性允许将该化合物用作化学交换饱和转移(CEST)对比剂。质子/质子敏感性增强因子每个伊米诺质子质子超过5000,允许检测一些微摩尔的聚合物(2000尿苷单元; 644 kD),水信号变化了50%。在较低的浓度下,增强因子将进一步增加,从而开放亚摩尔摩尔范围。当将poly(ru)复合到带有250个正电荷的树枝状聚合物时,对于10个树枝状聚合物,化学计量学约为一个RNA。敏感性增强降低,但保持较大(2300/伊米诺质子),从而增强了树枝状聚合物的可见性。该复合物的净电荷是正的,这表明复合的树突聚合物仍会与细胞膜相互作用,并且RNA树枝状聚合物复合物可以为具有良好CEST可见性的基因输送系统提供模型。 (c)2003 Wiley-Liss,Inc。
It is shown that the exchange properties of the imino and hydroxyl protons of polyuridilic acid (poly(rU)) allow use of this compound as a chemical-exchange saturation transfer (CEST) contrast agent. A proton/proton sensitivity enhancement factor of over 5000 per imino proton allowed the detection of a few micromolar of polymer (2000 uridine units; 644 kD) with a 50% change in the water signal. The enhancement factor would increase further at even lower concentrations, opening up the submicromolar range. When poly(rU) was complexed to a dendrimer carrying 250 positive charges, the stoichiometry was approximately one RNA for 10 dendrimers. The sensitivity enhancement was reduced but remained large (2300/imino proton), bringing enhanced CEST visibility to the dendrimers. The net charge of the complex was positive, suggesting that the complexed dendrimers would still interact with cell membranes, and that the RNA-dendrimer complex could provide a model for a gene delivery system with good CEST visibility. (C) 2003 Wiley-Liss, Inc.