School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK; School of Biochemistry, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK; BrisSynBio, University of Bristol, Life Sciences Building, Tyndall Avenue, Bristol BS8 1TQ, UK.
Curr Opin Biotechnol. 2019 Aug;58:175-182. doi: 10.1016/j.copbio.2019.03.017. Epub 2019 Apr 28.
One approach to designing de novo proteinaceous assemblies and materials is to develop simple, standardised building blocks and then to combine these symmetrically to construct more-complex higher-order structures. This has been done extensively using β-structured peptides to produce peptide fibres and hydrogels. Here, we focus on building with de novo α-helical peptides. Because of their self-contained, well-defined structures and clear sequence-to-structure relationships, α helices are highly programmable making them robust building blocks for biomolecular construction. The progress made with this approach over the past two decades is astonishing and has led to a variety of de novo assemblies, including discrete nanoscale objects, and fibrous, nanotube, sheet and colloidal materials. This body of work provides an exceptionally strong foundation for advancing the field beyond in vitro design and into in vivo applications including what we call protein design in cells.
设计全新的蛋白质组装体和材料的一种方法是开发简单、标准化的构建块,然后通过对称组合这些构建块来构建更复杂的高阶结构。这种方法已经被广泛应用于β结构肽,用于生产肽纤维和水凝胶。在这里,我们专注于使用全新的α-螺旋肽进行构建。由于它们具有自包含的、定义明确的结构和清晰的序列-结构关系,α 螺旋具有高度的可编程性,使它们成为生物分子构建的强大构建块。在过去二十年中,这种方法取得的进展令人惊讶,已经导致了各种全新的组装体,包括离散的纳米级物体以及纤维状、纳米管状、片状和胶体材料。这一工作为推进该领域从体外设计到体内应用,包括我们所说的细胞内蛋白质设计,提供了一个非常强大的基础。