Samad Mehdi Bin, Maddeboina Krishnaiah, Rodrigues de Almeida Nathalia, Conda-Sheridan Martin
Department of Pharmaceutical Sciences, University of Nebraska Medical Center.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center;
J Vis Exp. 2018 Jun 25(136):57908. doi: 10.3791/57908.
Polyamine-based Peptide Amphiphiles (PPAs) are a new class of self-assembling amphiphilic biomaterials-related to the peptide amphiphiles (PAs). Traditional PAs possess charged amino acids as solubilizing groups (lysine, arginine), which are directly connected to a lipid segment or can contain a linker region made of neutral amino acids. Tuning the peptide sequence of PAs can yield diverse morphologies. Similarly, PPAs possess a hydrophobic segment and neutral amino acids, but also contain polyamine molecules as water solubilizing (hydrophilic) groups. As is the case with PAs, PPAs can also self-assemble into diverse morphologies, including small rods, twisted nano-ribbons, and fused nano-sheets, when dissolved in water. However, the presence of both primary and secondary amines on a single polyamine molecule poses a significant challenge when synthesizing PPAs. In this paper, we show a simple protocol, based on literature precedents, to achieve a facile synthesis of PPAs using solid phase peptide synthesis (SPPS). This protocol can be extended to the synthesis of PAs and other similar systems. We also illustrate the steps that are needed for cleavage from the resin, identification, and purification.
基于多胺的肽两亲分子（PPA）是一类新型的自组装两亲生物材料，与肽两亲分子（PA）相关。传统的PA具有带电荷的氨基酸作为增溶基团（赖氨酸、精氨酸），这些基团直接连接到脂质片段上，或者可以包含由中性氨基酸组成的连接区域。调整PA的肽序列可以产生多种形态。同样，PPA具有疏水片段和中性氨基酸，但还含有多胺分子作为水溶性（亲水）基团。与PA一样，PPA溶解于水时也能自组装成多种形态，包括小棒状、扭曲的纳米带和融合的纳米片。然而，在合成PPA时，单个多胺分子上同时存在伯胺和仲胺带来了重大挑战。在本文中，我们基于文献先例展示了一种简单的方案，通过固相肽合成（SPPS）实现PPA的简便合成。该方案可以扩展到PA和其他类似体系的合成。我们还阐述了从树脂上切割、鉴定和纯化所需的步骤。
