Dong He, Paramonov Sergey E, Aulisa Lorenzo, Bakota Erica L, Hartgerink Jeffrey D
Departments of Chemistry and Bioengineering, Rice University, 6100 Main Street, Houston, Texas 77005, USA.
J Am Chem Soc. 2007 Oct 17;129(41):12468-72. doi: 10.1021/ja072536r. Epub 2007 Sep 26.
A series of nine, frustrated, multidomain peptides is described in which forces favoring self-assembly 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 beta-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 peptides eventually growing into high aspect ratio fibers. B block assembly may continue infinitely or until monomeric peptides 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 +/- 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.
本文描述了一系列九个受挫的多结构域肽，其中有利于自组装成纳米纤维的力与有利于解组装的力可以很容易地改变。这些肽被组织成ABA嵌段基序，其中中央B嵌段由交替的亲水和疏水氨基酸（分别为谷氨酰胺和亮氨酸）组成。这种交替使得氨基酸侧链在肽主链处于完全伸展的β-折叠构象时，能够在肽主链的相对两侧分离。在水中，两个这样的肽之间的堆积通过满足亮氨酸侧链将自身排除在水环境之外的愿望，稳定了伸展构象。一旦处于这种构象，额外肽之间很容易发生分子间主链氢键作用，最终生长成高纵横比的纤维。B嵌段组装可以无限期地继续，或者直到溶液中的单体肽耗尽，这会导致不溶性沉淀。A嵌段由可变数量的带正电荷的赖氨酸残基组成，其在pH 7时的静电排斥作用与B嵌段组装的愿望相悖。在这里，我们表明，平衡A嵌段和B嵌段的力，可以形成长度可控、单独分散且完全可溶的纳米纤维，其宽度为6±1纳米，长度为120±30纳米。通过红外、圆二色性和玻璃态冰冷冻透射电子显微镜分析表明，A嵌段和B嵌段的相对大小决定了肽的二级结构，进而控制了所得的纳米结构。所描述的系统体现了在有限自组装结构设计中分子受挫的应用。这些材料以及基于其结构的材料，可能会在需要对纤维结构和化学功能进行纳米结构控制的应用中找到用武之地。
