Understanding the protonation behavior of linear polyethylenimine in solutions through Monte Carlo simulations.
Understanding the protonation behavior of linear polyethylenimine in solutions through Monte Carlo simulations.
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DOI：
10.1021/bm900842d
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发表时间：
2010-01-11
影响因子：
6.2
通讯作者：
Wang, Yongmei
中科院分区：
文献类型：
--
作者：
Ziebarth, Jesse D.;Wang, Yongmei
聚乙烯亚胺(PEI)作为一种非病毒载体的成功，归功于它的质子缓冲能力。尽管PEI在非基于病毒的基因传递中的应用引起了人们的极大兴趣，但PEI在溶液中的质子化行为还没有被很好地理解。早期的实验研究已经报道了PEI的质子化状态的值不一致。在这项工作中，我们用计算方法研究了现实线性PEI(LPEI)的质子化行为。报道了几种二胺化合物的实验pKa值。屏蔽的库仑相互作用与距离相关的电介质能重现模型二胺化合物的pKa移动值。然后对含有20个重复单元的lPEI链进行了原子分子动力学模拟，模拟结果为粗粒多胺模型提供了参数。然后，将屏蔽的库仑相互作用并入粗粒lPEI链中，并进行计算滴定。LPEI在溶液中的计算滴定曲线与Smitts等人的实验结果符合得很好，但与Smitts等人的实验结果相比，计算滴定曲线对盐浓度的依赖性太强。忽略盐依赖性的差异，我们的计算滴定表明，在生理条件下，大约55%的lPEI胺基团在溶液中质子化，质子化和非质子化的胺几乎交替排列。还进行了在聚阴离子存在下的lPEI的滴定，以确定在基因治疗制剂中，lPEI的电荷状态如何受与DNA的络合作用的影响。虽然聚阴离子的存在增加了PEI的质子化程度，但许多PEI胺在生理条件下保持未质子化，这提供了PEI与DNA络合仍然具有质子缓冲能力的证据。还讨论了导致先前报道的PEI质子化状态不一致的潜在误差来源。
The success of polyethyleneimine (PEI) as a non-viral based gene delivery vector has been attributed to its proton buffering capacity. Despite the great interest in PEI for its use in non-viral based gene delivery, the protonation behavior of PEI in solution is not well understood. Earlier experimental studies have reported inconsistent values of the protonation state of PEI. In this work, we report our investigation of the protonation behavior of a realistic linear PEI (lPEI) with computational approaches. Reported experimental pKa values of several diamine compounds are first examined. A screened coulombic interaction with a distance dependence dielectric is shown to reproduce the shifted pKa values of the model diamine compounds. Then atomistic molecular dynamics simulations of lPEI chain with 20 repeating units are performed and the results are used to provide parameters for a coarse-grained polyamine model. The screened coulombic interaction is then incorporated in the coarse-grained lPEI chain and computational titrations are performed. The obtained computational titration curves of lPEI in solutions were found to be in best agreement with experimental results by Smits et al, but the computational titration curves have too strong of a dependence on salt concentration compared to the experimental results by Smits et al. Disregarding the discrepancy in the salt dependence, our computational titrations reveal that approximately 55% of the lPEI amine groups are protonated under physiological conditions in solution with a nearly alternating arrangement of protonated and non-protonated amines. Titrations of lPEI in the presence of a polyanion are also performed to determine how the charge state of lPEI could be affected by complexation with DNA in gene therapy preparations. While the presence of the polyanion increases the degree of protonation of the PEI, many of PEI amines remain unprotonated under physiological conditions, providing evidence that PEI complexed with DNA could still have proton buffering capacity. Potential sources of error that have resulted in the inconsistency of previously reported protonation states of PEI were also discussed.
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影响因子：
2.9
作者：
BASHFORD, D;KARPLUS, M
通讯作者：
KARPLUS, M
DOI：
10.1039/p29800001105
发表时间：
1980-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子：
--
作者：
JAMESON, RF;HUNTER, G;KISS, T
通讯作者：
KISS, T
影响因子：
5.5
作者：
Koper, GJM;van Duijvenbode, RC;Borkovec, A
通讯作者：
Borkovec, A
影响因子：
6
作者：
Laguecir, Abohachem;Ulrich, Serge;Buffle, Jacques
通讯作者：
Buffle, Jacques
影响因子：
5.5
作者：
KITANO, T;KAWAGUCHI, S;MINAKATA, A
通讯作者：
MINAKATA, A