Department of Soft Matter Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
J Am Chem Soc. 2010 Feb 24;132(7):2370-7. doi: 10.1021/ja909540a.
A new class of peptide has been created, polypeptide-b-designed peptides, which unites the useful qualities of the two constituent peptide types. We demonstrate the synthesis and self-assembly possibilities of this class of peptide chimera with a series of amphiphilic polypeptide-b-designed peptides in which the hydrophobic block is poly(gamma-benzyl l-glutamate) (PBLG) and the hydrophilic block is a coiled-coil forming peptide (denoted E). The synthetic approach was to synthesize the coiled-coil forming peptide on the solid phase, followed by the ring-opening polymerization of gamma-benzyl l-glutamate N-carboxyanhydride, initiated from the N-terminal amine of the peptide E on the solid support. The polypeptide-b-peptide was then cleaved from the resin, requiring no further purification. Peptide E contains 22 amino acids, while the average length of the PBLG block ranged from 36 to 250 residues. This new class of peptide was applied to create a modular system, which relied on juxtaposing the properties of the component peptide types, namely the broad size range and structure-inducing characteristics of the polypeptide PBLG blocks, and the complex functionality of the sequence-designed peptide. Specifically, the different PBLG block lengths could be connected noncovalently with various hydrophilic blocks via the specific coiled-coil folding of E with K or K-poly(ethylene glycol), where K is a peptide of complementary amino acid sequence to E. In this way, nanostructures could be formed in water at neutral pH over the entire compositional range, which has not been demonstrated previously with such large PBLG blocks. It was found that the size, morphology (polymersomes or bicelles), and surface functionality could be specified by combining the appropriate modular building blocks. The self-assembled structures were characterized by dynamic light scattering, circular dichroism, scanning electron microscopy, cryogenic-transmission electron microscopy, fluorescence spectroscopy, and zeta-potential measurements. Finally, as the structures are able to encapsulate water-soluble compounds, and the surfaces are easily functionalized via the coiled-coil binding, it is expected that these peptide-based nanocapsules will be able to act as delivery vehicles to specific targets in the body.
已经创建了一类新的肽，即多肽-b-设计肽，它结合了两种组成肽类型的有用特性。我们用一系列两亲性多肽-b-设计肽展示了这种肽嵌合体的合成和自组装可能性，其中疏水链段为聚(γ-苄基 L-谷氨酸)(PBLG)，亲水链段为卷曲螺旋形成肽(表示为 E)。合成方法是在固相上合成卷曲螺旋形成肽，然后用 γ-苄基 L-谷氨酸 N-羧酸酐开环聚合，从固相上肽 E 的 N 端胺引发聚合。然后将多肽-b-肽从树脂上裂解下来，无需进一步纯化。肽 E 含有 22 个氨基酸，而 PBLG 链段的平均长度从 36 到 250 个残基不等。这种新型肽被应用于创建一个模块化系统，该系统依赖于组合组成肽类型的特性，即多肽 PBLG 链段的广泛尺寸范围和结构诱导特性，以及序列设计肽的复杂功能。具体来说，不同的 PBLG 链段长度可以通过 E 与 K 或 K-聚(乙二醇)的特定卷曲螺旋折叠非共价连接各种亲水链段，其中 K 是与 E 互补氨基酸序列的肽。通过这种方式，可以在中性 pH 的水中形成整个组成范围内的纳米结构，这在以前使用如此大的 PBLG 链段时从未得到证明。研究发现，通过组合适当的模块化构建块，可以指定尺寸、形态(聚合物囊泡或双脂体)和表面功能。通过动态光散射、圆二色性、扫描电子显微镜、低温透射电子显微镜、荧光光谱和 ζ-电位测量对自组装结构进行了表征。最后，由于这些结构能够包裹水溶性化合物，并且表面可以通过卷曲螺旋结合轻松功能化，因此预计这些基于肽的纳米胶囊将能够作为载体将特定的药物递送到体内的特定目标。
