【摘要】 以螺旋型抗菌肽HPRP-A1为模板,利用精氨酸(R)对HPRP-A1序列中的赖氨酸(K)进行不同位点、不同数量的取代,结合改造前后抗菌肽的螺旋度、疏水性及自聚集常数等理化性质,研究了螺旋型抗菌肽结构与活性的相关性.进一步结合脂质体模拟和细胞膜穿透实验,对螺旋型抗菌肽与不同类型细胞膜的相互作用过程进行了研究.结果表明,增加精氨酸的取代数量,会增强抗菌肽的疏水性和螺旋度,导致螺旋型抗菌肽对真核细胞的毒性增强;但精氨酸的增加会伴随着抗菌肽自聚集能力的降低以及抗菌肽对细菌细胞膜的渗透性降低,导致抗菌肽的抗菌活性降低.本研究对于设计和改造具有应用前景的螺旋型抗菌肽具有重要指导意义.更多还原

【Abstract】 In order to investigate the effect of basic amino acids on the biological activity of antimicrobial peptides,an α helical antimicrobial peptides of HPRP-A1 was used to design several peptide derivatives with different K/R ratio by substitution lysine( K) with arginine( R). The relationship between the structure and activity of helical antimicrobial peptides was studied by combining the biophysical properties such as helicity,hydrophobicity and peptide association parameter of antimicrobial peptides. The interaction between helical antimicrobial peptides and different types of cell membranes was further studied by liposome mimic membrane and the cell permeation ability of peptide was examined by 1-N-pbenyl-naphtylamine( NPN) and o-nitrophenyl-β-D-galactopyranoside( ONPG). The results confirmed that the increasing numbers of arginine substitution increased the hydrophobicity and helicity of the antimicrobial peptides,resulting in increasing toxicity of the helical antimicrobial peptides against eukaryotic cell membrane. However,the increasing of arginine was accompanied by decreasing in the ability of peptide association and the permeability of the antimicrobial peptide against the prokaryotic cell membrane,resulting in decreasing of the antibacterial activity of the antimicrobial peptide.更多还原