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手性药物在β-折叠肽自组装支架中的控制释放和包埋。

Controlled release and entrapment of enantiomers in self-assembling scaffolds composed of beta-sheet peptides.

机构信息

Department of Materials Science and Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan.

出版信息

Biomacromolecules. 2009 Dec 14;10(12):3266-72. doi: 10.1021/bm900857j.

DOI:10.1021/bm900857j
PMID:19904950
Abstract

As a first step toward utilizing self-assembling peptide scaffolds to create tunable matrices for drug delivery, peptide RADAFI and RADAFII, containing the same amino acid composition but different positions of one phenylalanine residue, scaffolds were prepared for controlled release of chiral enantiomers. The release behaviors depended on the network nanostructures and the guest chirality and were well tailored via loading different amounts of guests. This contribution addressed the relationships among the peptide sequence, the network nanoarchitecture, and the controlled release. RADAFII systems provided a means of controlling the release kinetics for L- and D-phenylalanine, which was achieved through the facile pi-pi stacking between the aromatic rings of L-isomer and those in RADAFII sequence and through the appropriate scaffold nanoarchitecture. The concept of controlled release for enantiomers via dominating the network nanostructures can also be harnessed in the de novo design of delivery systems with specific structural features for some special biomolecules.

摘要

作为利用自组装肽支架为药物传递创建可调谐基质的第一步,我们制备了含有相同氨基酸组成但一个苯丙氨酸残基位置不同的肽 RADAFI 和 RADAFII 支架,以控制手性对映异构体的释放。释放行为取决于网络纳米结构和客体手性,并通过加载不同量的客体进行了很好的调整。本研究探讨了肽序列、网络纳米结构和控制释放之间的关系。RADAFII 系统为 L-和 D-苯丙氨酸的释放动力学提供了一种控制手段,这是通过 L-异构体的芳香环与 RADAFII 序列中的芳香环之间的易于形成的π-π堆积以及适当的支架纳米结构实现的。通过控制网络纳米结构控制对映异构体释放的概念也可以应用于具有某些特殊生物分子的特定结构特征的新型递药系统的设计中。

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