Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia 30322, United States.
J Am Chem Soc. 2013 Oct 16;135(41):15565-78. doi: 10.1021/ja4074529. Epub 2013 Oct 3.
Design of a structurally defined helical assembly is described that involves recoding of the amino acid sequence of peptide GCN4-pAA. In solution and the crystalline state, GCN4-pAA adopts a 7-helix bundle structure that resembles a supramolecular lock washer. Structurally informed mutagenesis of the sequence of GCN4-pAA afforded peptide 7HSAP1, which undergoes self-association into a nanotube via noncovalent interactions between complementary interfaces of the coiled-coil lock-washer structures. Biophysical measurements conducted in solution and the solid state over multiple length scales of structural hierarchy are consistent with self-assembly of nanotube structures derived from 7-helix bundle subunits. The dimensions of the supramolecular assemblies are similar to those observed in the crystal structure of GCN4-pAA. Fluorescence studies of the interaction of 7HSAP1 with the solvatochromic fluorophore PRODAN indicated that the nanotubes could encapsulate shape-appropriate small molecules with high binding affinity.
描述了一种结构确定的螺旋组装的设计，该设计涉及对肽 GCN4-pAA 的氨基酸序列进行重新编码。在溶液中和晶体状态下，GCN4-pAA 采用 7 螺旋束结构，类似于超分子锁垫圈。对 GCN4-pAA 的序列进行结构信息指导的诱变得到了肽 7HSAP1，它通过螺旋锁垫圈结构的互补界面之间的非共价相互作用自组装成纳米管。在溶液中和固体状态下进行的多个结构层次的生物物理测量与源自 7 螺旋束亚基的纳米管结构的自组装一致。超分子组装的尺寸与在 GCN4-pAA 的晶体结构中观察到的尺寸相似。7HSAP1 与溶剂化变色荧光团 PRODAN 的相互作用的荧光研究表明，纳米管可以高结合亲和力包封形状合适的小分子。
