蜂毒肽类似物的抗菌活性和溶血活性研究.pdfVIP

蜂毒肽类似物的抗菌活性和溶血活性 阎虎生，李顺子，孙学军，密怀风 （南开大学高分子化学研究所，功能高分子材料教育部重点实验室，天津 300071，中国） 摘要： 存在于各种生物体内的抗菌多肽及其类似物作为抗耐药细菌的新型抗菌素已引起高度关注，一些抗菌 肽还具有溶血活性。文献报道认为这些肽的两亲性α-螺旋结构对抗菌和溶血都是关键因素。为了研究蜂毒肽 C 端 15 氨基酸片段(M(12-26))的亲水-疏水性对抗菌和溶血活性的影响，M(12-26)的1-9 位氨基酸的极性通过 残基逐一取代而改变。结果表明，几乎所有取代位置上的疏水性的增大使抗菌活性增加，影响较大和较小的 位置正好处于多肽的螺旋轮投影图的相反的两侧，表明抗菌肽的疏水性和其方向性而非两亲性是抗菌活性的 关键因素。相反，α-螺旋结构的一侧的疏水性对溶血是有利的，而另一侧是不利的，表明两亲性对溶血活性 是重要的。更有趣的发现是，疏水性对抗菌活性有利的一侧与对溶血活性有利的一侧正好处于相反的方向。 关键词：蜂毒肽；抗菌肽；抗菌；溶血；疏水性；两亲性 Effects of Hydropathicities of Melittin Analogues on the Antimicrobial and Hemolytic Activities YAN Husheng, LI Shunzi, SUN Xuejun, MI Huaifeng Key Laboratory of Function Polymer Materials, Ministry of Educastion, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China Abstract: The development of bacterial resistance to traditional antibiotics has reached alarming levels, making it essential that new antibiotics be developed. The endogenous antimicrobial peptides, which are widespread in nature occurring in animals, plants and bacterial species, and their analogues have been considered as good candidates of such antibiotics. Some of the antimicrobial peptides also possess hemolytic activity. Amphipathic α-helical structures of these peptides have been believed to be crucial for both antimicrobial activity and hemolytic activity. Melittin, the major component of honey bee (Apis mellifera) venom, possesses a broad antibacterial activity and very high hemolytic activity. In order to study the effect of the hydropathicity of M(12-26), the C-terminal 15-residue segment of melittin, on the antimicrobial and hemolytic activities, the residues 1-9 of M(12-26) were substituted individually to change the hydropathicities in these positions. The antimicrobial and hemolytic activities of these peptides were determ