Department of Pharmacy, University of Naples "Federico II", Italy.
Center for Advanced Biomaterial for Health Care (CABHC), Istituto Italiano di Tecnologia, Naples, Italy; Interdisciplinary Research Centre on Biomaterials (CRIB), Department of Ingegneria Chimica del Materiali e della Produzione Industriale (DICMAPI), University "Federico II", Piazzale Tecchio 80, 80125 Naples, Italy.
Bioorg Chem. 2021 Sep;114:105047. doi: 10.1016/j.bioorg.2021.105047. Epub 2021 May 30.
Peptide hydrogels, deriving from natural protein fragments, present unique advantages as compatibility and low cost of production that allow their wide application in different fields as wound healing, cell delivery and tissue regeneration. To engineer new biomaterials, the change of the chirality of single amino acids demonstrated a powerful approach to modulate the self-assembly mechanism. Recently we unveiled that a small stretch spanning residues 268-273 in the C-terminal domain (CTD) of Nucleophosmin 1 (NPM1) is an amyloid sequence. Herein, we performed a systematic D-scan of this sequence and analyzed the structural properties of obtained peptides. The conformational and kinetic features of self-aggregates and the morphologies of derived microstructures were investigated by means of different biophysical techniques, as well as the compatibility of hydrogels was evaluated in HeLa cells. All the investigated hexapeptides formed hydrogels even if they exhibited different conformational intermediates during aggregation, and they structural featured are finely tuned by introduced chiralities.
肽水凝胶来源于天然蛋白质片段，具有良好的生物相容性和较低的生产成本，在伤口愈合、细胞递送和组织再生等多个领域得到了广泛应用。为了设计新型生物材料，改变单个氨基酸的手性是一种有效的方法，可以调节自组装机制。最近，我们揭示了核仁磷酸蛋白 1（NPM1）C 端结构域（CTD）中残基 268-273 之间的一小段肽序列是淀粉样肽序列。在此，我们对该序列进行了系统的 D 扫描，并分析了所得肽的结构特性。通过不同的生物物理技术研究了自聚集的构象和动力学特性以及衍生的微结构的形态，还评估了水凝胶在 HeLa 细胞中的相容性。所有研究的六肽都形成了水凝胶，即使它们在聚集过程中表现出不同的构象中间体，而且通过引入手性还可以精细调节它们的结构特征。
