Department of Chemistry, Indian Institute of Technology Kharagpur , Kharagpur 721 302, India.
Department of Chemistry and Institute for Soft Matter Synthesis and Metrology, Georgetown University , Washington, D.C. 20057-1227, United States.
Langmuir. 2017 Nov 14;33(45):12989-12999. doi: 10.1021/acs.langmuir.7b03018. Epub 2017 Nov 3.
A series of β-amino acid containing tripeptides has been designed and synthesized in order to develop oligopeptide-based, thermoreversible, pH-sensitive, and proteolytically stable hydrogels. The Fmoc [N-(fluorenyl-9-methoxycarbonyl)]-protected tripeptides were found to produce hydrogels in both pH 7 and 2 buffers at a very low concentration (<0.2% w/v). It has been shown that the Fmoc group plays an important role in the gelation process. Also a dependence of gelation ability on hydrophobicity of the side chain of the Fmoc-protected α-amino acid was observed. The effect of the addition of inorganic salts on the gelation process was investigated as well. Spectroscopic studies indicated formation of J-aggregates through π-π stacking interactions between Fmoc groups in solution as well as in the gel state. In the gel phase, these self-assembling tripeptides form long interconnected nanofibrils leading to the formation of 3-dimensional network structure. The hydrogels were characterized by various techniques, including field emission electron microscopy, transmission electron microscopy, atomic force microscopy, rheology, Fourier transform IR, circular dichroism (CD), and wide-angle X-ray diffraction (WAXD) spectroscopy. The CD studies and WAXD analyses show an antiparallel β-sheet structure in the gel state. l-Phenylalanine and l-tyrosine containing tripeptides formed helical aggregates with handedness opposite to those containing l-valine and l-leucine residues. The mechanical stability of the hydrogels was found to depend on the hydrophobicity of the side chain of the tripeptide as well as on the pH of the solution. Also, the tripeptides exhibit in vitro proteolytic stability against proteinase K enzyme.
为了开发基于寡肽的热可逆、pH 敏感和蛋白水解稳定的水凝胶，设计并合成了一系列含有β-氨基酸的三肽。Fmoc[N-(芴甲氧羰基)]保护的三肽在 pH 7 和 2 的缓冲液中，浓度非常低（<0.2%w/v）时即可形成水凝胶。研究表明，Fmoc 基团在凝胶化过程中起着重要作用。此外，还观察到 Fmoc-保护的α-氨基酸侧链疏水性对凝胶能力的依赖性。还研究了添加无机盐对凝胶化过程的影响。光谱研究表明，在溶液中和凝胶状态下，Fmoc 基团通过π-π堆积相互作用形成 J-聚集体。在凝胶相中，这些自组装三肽形成长的相互连接的纳米纤维，导致 3 维网络结构的形成。水凝胶通过各种技术进行了表征，包括场发射电子显微镜、透射电子显微镜、原子力显微镜、流变学、傅里叶变换红外光谱、圆二色性（CD）和广角 X 射线衍射（WAXD）光谱。CD 研究和 WAXD 分析表明在凝胶状态下存在反平行β-折叠结构。含 l-苯丙氨酸和 l-酪氨酸的三肽形成了手性与含 l-缬氨酸和 l-亮氨酸残基的三肽相反的螺旋聚集体。水凝胶的机械稳定性取决于三肽侧链的疏水性以及溶液的 pH 值。此外，三肽对蛋白酶 K 酶表现出体外蛋白水解稳定性。
