烷基链长及肽链电荷分布对脂肽双亲分子自组装及水凝胶化的影响

为阐明脂肽分子烷基链长及肽链电荷分布对其自组装及水凝胶化的影响, 设计合成了C_nV₃K₂ (n=12, 14, 16) 和C_mKV₃K (m=14, 16)两个系列的脂肽分子. 原子力显微镜(AFM)和透射电镜(TEM)结果表明, 两个系列的脂肽分子都可以自组装成一维纳米带结构. 圆二色(CD)光谱结果表明, C_nV₃K₂系列自组装体的二级结构为β折叠; C_mKV₃K系列自组装体中包括α螺旋和β折叠两种二级结构, 其中C14KV3K的α螺旋结构较多, C16KV3K的β折叠结构占优. 烷基链疏水作用的增强会抑制β折叠结构侧向堆积, 使纳米带随烷基链的变长而变窄; 电荷分布于肽链部分的两端有利于纳米带结构的侧向生长. 流变性测试结果表明, 在浓度10 mmol·L^-1、pH 8.4下, 脂肽分子可以形成自支撑水凝胶, 相比烷基链长度, 肽链部分的电荷分布对水凝胶性能影响更大.

Effects of Alkyl Chain Length and Peptide Charge Distribution on Self-Assembly and Hydrogelation of Lipopeptide Amphiphiles

The self-assembly and hydrogelation of two series of lipopeptide amphiphiles, C_nV₃K₂ (n=12, 14, 16) and C_mKV₃K (m=14, 16), were studied to determine the effects of alkyl chain length and peptide charge distribution. Both the transmission electron microscopy (TEM) and atomic force microscopy (AFM) results showed that all lipopeptide molecules in both series self-assembled into nanotapes with a bilayer structure. The width of the nanotapes decreased with increasing alkyl chain lengths. At a given alkyl chain length, the width of the C_mKV₃K nanotapes was wider than that of the C_nV₃K₂ nanotapes. Based on the circular dichroism (CD) spectra of the nanotapes, all three C_nV₃K₂ molecules adopted a secondary structure of β sheet. In contrast, the secondary structure of the C_mKV₃K nanotapes comprised a mixture of α helix and β sheet. For C14KV3K, the content of the α helix structures was higher than that of the β sheet structures. Conversely, for C16KV3K, the content of the β sheet was higher than that of the α helix structures. The nanotapes of lipopeptides with long alkyl chains were narrower than those with short chains, suggesting that the increased alkyl chain hydrophobicity inhibited lateral stacking of β sheets. When compared with C_nV₃K₂, of which the two positive charges are arranged at the carbon terminal, the separate arrangement of the two positive charges in C_mKV₃K reduced electrostatic repulsion and favored lateral stacking of β sheets to produce wider nanotapes. The rheological data showed that all lipopeptides formed self-supporting hydrogels at 10 mmol·L^-1 and pH 8.4. The hydrogel strength of the lipopeptides with different alkyl chain lengths was nearly the same within a given series. Furthermore, the hydrogel strength of the lipopeptides in the C_mKV₃K series was higher than that of the lipopeptides in the C_nV₃K₂ series. The results indicated that the hydrogel rheological property was more influenced by charge arrangement at the peptide segment than by the alkyl chain length. Also, pH influenced to a great extent the self-assembly of the lipopeptides. The lipopeptides in the C_mKV₃K series were more sensitive to pH than those in the C_nV₃K₂ series.