Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str. 10, Berlin, 10623, Germany.
Org Biomol Chem. 2019 Feb 27;17(9):2502-2507. doi: 10.1039/c9ob00070d.
In contrast to many other water-soluble peptide arrangements, the formation of a triple helix in collagen proceeds inside out: polar glycyl residues form the interior, whereas nonpolar prolyl side chains constitute the exterior. In our work, we decided to exploit this aspect of the peptide architecture in order to create hyperstable collagen mimicking peptides (CMPs). The key element of this study is the environment. Given that the peptide assembles in a nonpolar medium, the collapse of the polar peptide backbone into the triple helix should become more favorable. Following this idea, we prepared CMPs based on hydrophobic proline analogues. The synthesis was performed by a combination of liquid- and solid-phase approaches: first, hexapeptides were prepared in solution, and then these were launched into conventional Fmoc-based peptide synthesis on a solid support. The resulting peptides showed an excellent signal of the triple helix in the model nonpolar solvent (octanol) according to circular dichroism observations. In a study of a series of oligomers, we found that the minimal length of the peptides required for triple helical assembly is substantially lower compared to water-soluble CMPs. Our results suggest further explorations of the CMPs in hydrophobic media; in particular, we highlight the suggestion that collagen could be converted into a membrane protein.
与许多其他水溶性肽排列不同，胶原蛋白中三螺旋的形成是从内到外进行的：极性甘氨酰残基形成内部，而非极性脯氨酸侧链构成外部。在我们的工作中，我们决定利用肽结构的这一方面来创建超稳定的胶原蛋白模拟肽（CMP）。这项研究的关键要素是环境。鉴于肽在非极性介质中组装，极性肽骨架折叠成三螺旋应该变得更加有利。基于这个想法，我们基于疏水性脯氨酸类似物制备了 CMP。合成是通过液相和固相方法的组合来完成的：首先，在溶液中制备六肽，然后将其在固体载体上进行常规的 Fmoc 基肽合成。根据圆二色性观察，所得肽在模型非极性溶剂（辛醇）中显示出三螺旋的优异信号。在一系列低聚物的研究中，我们发现与水溶性 CMP 相比，三螺旋组装所需的肽的最小长度要低得多。我们的结果表明需要进一步在疏水环境中探索 CMP；特别是，我们强调了胶原蛋白可以转化为膜蛋白的建议。
