Bellotto Ottavia, Pierri Giovanni, Rozhin Petr, Polentarutti Maurizio, Kralj Slavko, D'Andrea Paola, Tedesco Consiglia, Marchesan Silvia
University of Trieste, Chem. Pharm. Sc. Dept., Via Giorgieri 1, 34127 Trieste, Italy.
University of Salerno, Dept. of Chemistry & Biologi "A. Zambelli", Via Giovanni Paolo II 132, 84084 Fisciano, SA, Italy.
Org Biomol Chem. 2022 Aug 10;20(31):6211-6218. doi: 10.1039/d2ob00622g.
Dipeptides are convenient building blocks for supramolecular gel biomaterials that can be produced on a large scale at low cost and do not persist in the environment. In the case of unprotected sequences, hydrophobicity is a key requirement to enable gelation, with Phe-Phe standing out for its self-assembling ability. Conversely, more hydrophilic sequences such as homochiral dipeptides Phe-Val and Val-Phe neither fibrillate nor gel aqueous buffers and their crystal structures reveal amphipathic layers. In this work, we test emerging rules for the design of self-assembling dipeptides using heterochiral Phe-Val and Val-Phe. Each dipeptide is characterized by H- and C-NMR, LC-MS, circular dichroism, infrared and Raman spectroscopies, rheology, electron microscopy, and single-crystal X-ray diffraction. In particular, D-Phe-L-Val is the first heterochiral dipeptide to self-assemble into supramolecular water-channels whose cavity is defined by four peptide molecules arranged head-to-tail. This minimalistic sequence is devoid of amyloid character as probed by thioflavin T fluorescence and it displays excellent biocompatibility . The dataset provided, through comparison with the literature, significantly advances the definition of molecular design rules for minimalistic unprotected dipeptides that self-assemble into water-channels and biocompatible gels, to assist with the future development of supramolecular biomaterials with fine control over nanomorphological features for a variety of applications.
二肽是超分子凝胶生物材料方便的构建单元，它们可以低成本大规模生产且不会在环境中持久存在。对于未受保护的序列，疏水性是实现凝胶化的关键要求，其中苯丙氨酸 - 苯丙氨酸因其自组装能力而格外突出。相反，更具亲水性的序列，如同手性二肽苯丙氨酸 - 缬氨酸和缬氨酸 - 苯丙氨酸，既不会形成纤维也不会使水性缓冲液凝胶化，并且它们的晶体结构显示出两亲性层。在这项工作中，我们使用杂手性的苯丙氨酸 - 缬氨酸和缬氨酸 - 苯丙氨酸测试自组装二肽设计的新规则。每个二肽通过氢和碳核磁共振、液相色谱 - 质谱联用、圆二色性、红外和拉曼光谱、流变学、电子显微镜以及单晶X射线衍射进行表征。特别是，D - 苯丙氨酸 - L - 缬氨酸是第一个自组装成超分子水通道的杂手性二肽，其通道由四个首尾相连排列的肽分子定义。通过硫黄素T荧光探测，这个简约的序列没有淀粉样蛋白特征，并且显示出优异的生物相容性。通过与文献比较提供的数据显著推进了对简约未受保护二肽分子设计规则的定义，这些二肽自组装成水通道和生物相容性凝胶，以协助未来超分子生物材料的开发，从而对各种应用的纳米形态特征进行精细控制。
