Self-assembly of multidomain peptides: Balancing molecular frustration controls conformation and nanostructure
Self-assembly of multidomain peptides: Balancing molecular frustration controls conformation and nanostructure
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DOI：
10.1021/ja072536r
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发表时间：
2007-10-17
影响因子：
15
通讯作者：
Hartgerink, Jeffrey D.
中科院分区：
文献类型：
--
作者：
Dong, He;Paramonov, Sergey E.;Hartgerink, Jeffrey D.
本文描述了一系列九种受挫的多结构域肽，其中有利于自组装成纳米纤维的力与那些有利于拆卸的力可以很容易地进行修饰。这些肽被组织成ABA块基序，其中中央B块由亲水性和疏水性氨基酸交替组成（分别为谷氨酰胺和亮氨酸）。当肽处于完全延伸的P-sheet构象时，这种交替允许氨基酸侧链在肽主链的两侧分离。在水中，两个这样的肽之间的填充通过满足亮氨酸侧链将自己排除在水环境之外的愿望来稳定扩展的构象。一旦在这种构象中，分子间的骨干氢键可以很容易地在额外的肽之间发生，最终生长成高纵横比纤维。B段组装可以无限地继续或直到单体颗粒从溶液中耗尽，从而导致不溶性沉淀。A区由数量可变的带正电赖氨酸残基组成，其在pH值为7时的静电斥力与B区组装的愿望相反。在这里，我们发现平衡A块和B块的力可以形成长度可控的、分散的、完全可溶的纳米纤维，宽度为6 +/- 1 nm，长度为120 - 1 30 nm。红外、圆二色性和玻璃冰晶透射电镜分析表明，A和B的相对大小决定了肽二级结构，从而控制了最终的纳米结构。所描述的系统集中体现了分子挫折在有限自组装结构设计中的应用。这些材料，以及基于其结构的材料，可能会在需要纳米结构控制纤维结构和化学功能的地方找到应用。
A series of nine, frustrated, multidomain peptides is described in which forces favoring selfassembly into a nanofiber versus those favoring disassembly could be easily modified. The peptides are organized into an ABA block motif in which the central B block is composed of alternating hydrophilic and hydrophobic amino acids (glutamine and leucine, respectively). This alternation allows the amino acid side chains to segregate on opposite sides of the peptide backbone when it is in a fully extended P-sheet conformation. In water, packing between two such peptides stabilizes the extended conformation by satisfying the desire of the leucine side chains to exclude themselves from the aqueous environment. Once in this conformation intermolecular backbone hydrogen bonding can readily take place between additional pepticles eventually growing into high aspect ratio fibers. B block assembly may continue infinitely or until monomeric pepticles are depleted from solution which results in an insoluble precipitate. Block A consists of a variable number of positively charged lysine residues whose electrostatic repulsion at pH 7 works against the desire of the B block to assemble. Here we show that balancing the forces of block A against B allows the formation of controlled length, individually dispersed, and fully soluble nanofibers with a width of 6 +/- 1 nm and length of 120 1 30 nm. Analysis by infrared, circular dichroism, and vitreous ice cryo-transmission electron microscopy reveals that the relative sizes of blocks A and B dictate the peptide secondary structure which in turn controls the resulting nanostructure. The system described epitomizes the use of molecular frustration in the design of finite self-assembled structures. These materials, and ones based on their architecture, may find applications where nanostructured control over fiber architecture and chemical functionality is required.