Agrahari Ashutosh, Lipton Mark, Chmielewski Jean
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
Nanomaterials (Basel). 2023 Sep 26;13(19):2645. doi: 10.3390/nano13192645.
Peptide-based helical barrels are a noteworthy building block for hierarchical assembly, with a hydrophobic cavity that can serve as a host for cargo. In this study, disulfide-stapled helical barrels were synthesized containing ligands for metal ions on the hydrophilic face of each amphiphilic peptide helix. The major product of the disulfide-stapling reaction was found to be composed of five amphiphilic peptides, thereby going from a 16-amino-acid peptide to a stapled 80-residue protein in one step. The structure of this pentamer, , was optimized in silico, indicating a significant hydrophobic cavity of ~6 Å within a helical barrel. Metal-ion-promoted assembly of the helical barrel building blocks generated higher order assemblies with a three-dimensional (3D) matrix morphology. The matrix was decorated with hydrophobic dyes and His-tagged proteins both before and after assembly, taking advantage of the hydrophobic pocket within the helical barrels and coordination sites within the metal ion-peptide framework. As such, this peptide-based biomaterial has potential for a number of biotechnology applications, including supplying small molecule and protein growth factors during cell and tissue growth within the matrix.
基于肽的螺旋桶是用于分级组装的值得关注的构建模块，其具有可作为货物宿主的疏水腔。在本研究中，合成了二硫键固定的螺旋桶，在每个两亲性肽螺旋的亲水面上含有金属离子的配体。发现二硫键固定反应的主要产物由五个两亲性肽组成，从而一步从16个氨基酸的肽转变为固定的80个残基的蛋白质。该五聚体的结构在计算机上进行了优化，表明螺旋桶内有一个约6 Å的显著疏水腔。金属离子促进的螺旋桶构建模块的组装产生了具有三维（3D）基质形态的高阶组装体。在组装之前和之后，利用螺旋桶内的疏水口袋和金属离子 - 肽框架内的配位位点，用疏水染料和组氨酸标记的蛋白质对基质进行修饰。因此，这种基于肽的生物材料在许多生物技术应用中具有潜力，包括在基质内的细胞和组织生长过程中提供小分子和蛋白质生长因子。
