Low-Density Lipoproteins and Human Serum Albumin as Carriers of Squalenoylated Drugs: Insights from Molecular Simulations,Molecular Pharmaceutics

当前位置： X-MOL 学术 › Mol. Pharmaceutics › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Low-Density Lipoproteins and Human Serum Albumin as Carriers of Squalenoylated Drugs: Insights from Molecular Simulations
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-01-17 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00952
Semen O. Yesylevskyy ₁ , Christophe Ramseyer ₂ , Mariia Savenko ₂ , Simona Mura ₃ , Patrick Couvreur ₃

Affiliation

We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs accumulate inside the LDL particles. This effect is promoted by the squalene moiety, which acts as an anchor and drives the hydrophilic drugs into the hydrophobic core of the LDL lipid droplet. Our data suggest that LDL particles could be a universal carriers of squalenoylated drugs in the bloodstream. Interaction of gemcitabine-squalene with human serum albumin (HSA) was also studied by ensemble of docking simulations. It is shown that HSA could also act as a passive carrier of this bioconjugate. It should be noted that the binding of squalene moiety to HSA was unspecific and did not occur in the binding pockets devoted to fatty acids.

中文翻译：

低密度脂蛋白和人血清白蛋白作为角鲨烯化药物的载体：分子模拟的见解

我们已经通过原子分子动力学模拟研究了三种临床上有前途的角鲨烯酰化药物（吉西他滨-角鲨烯，腺嘌呤-角鲨烯和阿霉素-角鲨烯）与低密度脂蛋白（LDL）的相互作用。结果表明，所有研究的角鲨烯化药物都在LDL颗粒内部积聚。该作用由角鲨烯部分促进，该角鲨烯部分起锚定作用，并将亲水性药物驱使到LDL脂质小滴的疏水核中。我们的数据表明，LDL颗粒可能是血液中角鲨烯化药物的通用载体。吉西他滨-角鲨烯与人血清白蛋白（HSA）的相互作用也通过对接模拟的集成进行了研究。结果表明，HSA还可以充当该生物结合物的被动载体。

更新日期：2018-01-17

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11