Department of Oral Biology, The Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 69978, Israel.
The Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv 69978, Israel.
ACS Nano. 2020 Aug 25;14(8):9990-10000. doi: 10.1021/acsnano.0c03085. Epub 2020 Aug 10.
Collagen, the most abundant protein in mammals, possesses notable cohesion and elasticity properties and efficiently induces tissue regeneration. The Gly-Pro-Hyp canonical tripeptide repeating unit of the collagen superhelix has been well-characterized. However, to date, the shortest tripeptide repeat demonstrated to attain a helical conformation contained 3-10 peptide repeats. Here, taking a minimalistic approach, we studied a single repeating unit of collagen in its protected form, Fmoc-Gly-Pro-Hyp. The peptide formed single crystals displaying left-handed polyproline II superhelical packing, as in the native collagen single strand. The crystalline assemblies also display head-to-tail H-bond interactions and an "aromatic zipper" arrangement at the molecular interface. The coassembly of this tripeptide, with Fmoc-Phe-Phe, a well-studied dipeptide hydrogelator, produced twisted helical fibrils with a polyproline II conformation and improved hydrogel mechanical rigidity. The design of these peptides illustrates the possibility to assemble superhelical nanostructures from minimal collagen-inspired peptides with their potential use as functional motifs to introduce a polyproline II conformation into hybrid hydrogel assemblies.
胶原蛋白是哺乳动物中含量最丰富的蛋白质，具有显著的内聚性和弹性，能够有效地诱导组织再生。胶原蛋白超螺旋的甘氨酸-脯氨酸-羟脯氨酸典型三肽重复单元已经得到了很好的描述。然而，迄今为止，被证明能够达到螺旋构象的最短三肽重复序列包含 3-10 个肽重复序列。在这里，我们采取了一种极简主义的方法，研究了胶原蛋白保护形式中的单个重复单元 Fmoc-甘氨酸-脯氨酸-羟脯氨酸。该肽形成了单晶，显示出左手聚脯氨酸 II 超螺旋堆积，就像天然胶原蛋白单链一样。结晶组装还显示出分子界面处的头尾氢键相互作用和“芳香拉链”排列。这种三肽与 Fmoc-苯丙氨酸-苯丙氨酸（一种研究充分的二肽水凝胶剂）共组装，生成了具有聚脯氨酸 II 构象的扭曲螺旋纤维，并提高了水凝胶的机械刚性。这些肽的设计说明了从最小的胶原蛋白启发肽组装超螺旋纳米结构的可能性，并有可能将聚脯氨酸 II 构象引入混合水凝胶组装体中作为功能基序。
