Jamasbi Elaheh, Batinovic Steven, Sharples Robyn A, Sani Marc-Antoine, Robins-Browne Roy Michael, Wade John D, Separovic Frances, Hossain Mohammed Akhter
School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, VIC, 3010, Australia.
Amino Acids. 2014 Dec;46(12):2759-66. doi: 10.1007/s00726-014-1833-9. Epub 2014 Sep 9.
Melittin (MLT) is a lytic peptide with a broad spectrum of activity against both eukaryotic and prokaryotic cells. To understand the role of proline and the thiol group of cysteine in the cytolytic activity of MLT, native MLT and cysteine-containing analogs were prepared using solid phase peptide synthesis. The antimicrobial and cytolytic activities of the monomeric and dimeric MLT peptides against different cells and model membranes were investigated. The results indicated that the proline residue was necessary for antimicrobial activity and cytotoxicity and its absence significantly reduced lysis of model membranes and hemolysis. Although lytic activity against model membranes decreased for the MLT dimer, hemolytic activity was increased. The native peptide and the MLT-P14C monomer were mainly unstructured in buffer while the dimer adopted a helical conformation. In the presence of neutral and negatively charged vesicles, the helical content of the three peptides was significantly increased. The lytic activity, therefore, is not correlated to the secondary structure of the peptides and, more particularly, on the propensity to adopt helical conformation.
蜂毒肽（MLT）是一种具有广泛活性的溶解肽，对真核细胞和原核细胞均有作用。为了解脯氨酸和半胱氨酸的巯基在MLT细胞溶解活性中的作用，采用固相肽合成法制备了天然MLT和含半胱氨酸的类似物。研究了单体和二聚体MLT肽对不同细胞和模型膜的抗菌及细胞溶解活性。结果表明，脯氨酸残基对抗菌活性和细胞毒性是必需的，其缺失会显著降低模型膜的裂解和溶血作用。虽然MLT二聚体对模型膜的溶解活性降低，但其溶血活性增加。天然肽和MLT - P14C单体在缓冲液中主要为无结构状态，而二聚体则呈现螺旋构象。在中性和带负电荷的囊泡存在下，这三种肽的螺旋含量显著增加。因此，溶解活性与肽的二级结构无关，更具体地说，与采用螺旋构象的倾向无关。
