Department of Pharmacy, Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Via Mezzocannone 16, 80134-Naples, Italy.
Department of Oral Biology, The Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, and the Center for Nanoscience and Nanotechnology Tel-Aviv University, 69978, Israel.
Soft Matter. 2020 Aug 5;16(30):7006-7017. doi: 10.1039/d0sm00825g.
Over the last few years, hydrogels have been proposed for many biomedical applications, including drug delivery systems and scaffolds for tissue engineering. In particular, peptides have been envisioned as excellent candidates for the development of hydrogel materials, due to their intrinsic biocompatibility, ease of handling, and intrinsic biodegradability. Recently, we developed a novel hybrid polymer-peptide conjugate, PEG8-(FY)3, which is able to self-assemble into a self-supporting soft hydrogel over dry and wet surfaces as demonstrated by molecular dynamics simulation. Here, we describe the synthesis and supramolecular organization of six novel hexapeptides rationally designed by punctual chemical modification of the primary peptide sequence of the ancestor peptide (FY)3. Non-coded amino acids were incorporated by replacing the phenylalanine residue with naphthylalanine (Nal) and tyrosine with dopamine (Dopa). We also studied the effect of the modification of the side chain and the corresponding PEGylated peptide analogues, on the structural and mechanical properties of the hydrogel. Secondary structure, morphology and rheological properties of all the peptide-based materials were assessed by various biophysical tools. The in vitro biocompatibility of the supramolecular nanostructures was also evaluated on fibroblast cell lines. We conclude that the PEG8-(Nal-Dopa)3 hydrogel possesses the right properties to serve as a scaffold and support cell growth.
在过去的几年中,水凝胶已经被提议用于许多生物医学应用,包括药物输送系统和组织工程支架。特别是,由于其内在的生物相容性、易于处理和内在的可生物降解性,肽被认为是开发水凝胶材料的优秀候选物。最近,我们开发了一种新型的混合聚合物-肽缀合物 PEG8-(FY)3,正如分子动力学模拟所证明的那样,它能够在干燥和潮湿的表面上自组装成自支撑的软水凝胶。在这里,我们描述了通过对原始肽 (FY)3 的序列进行定点化学修饰而合理设计的六个新型六肽的合成和超分子组织。通过用萘基丙氨酸 (Nal) 取代苯丙氨酸残基和用多巴胺 (Dopa) 取代酪氨酸来掺入非编码氨基酸。我们还研究了侧链修饰和相应的聚乙二醇化肽类似物对水凝胶的结构和机械性能的影响。通过各种生物物理工具评估了基于肽的所有材料的二级结构、形态和流变性能。还在成纤维细胞系上评估了超分子纳米结构的体外生物相容性。我们得出结论,PEG8-(Nal-Dopa)3 水凝胶具有作为支架和支持细胞生长的适当特性。