基于厚壳贻贝Mytilin-1的抗菌肽设计、固相合成及抗菌谱分析

Designation, solid-phase synthesis and antimicrobial activity of Mytilin derived peptides based on Mytilin-1 from Mytilus coruscus

摘要:

贻贝抗菌肽Mytilin是贻贝免疫系统的重要组成部分，对其结构与功能的研究表明，其序列中连接两段β-折叠的发夹区域是其抗菌功能的关键所在。为验证该区域是否具有抗菌活性，通过对厚壳贻贝Mytilus coruscus抗菌肽Mytilin进行空间结构模拟，选取其中β-发夹部分肽段，采用了固相化学合成的方法合成了两条10肽，分别命名为Mytilin Derived Peptide-1 (MDP-1) 和 Mytilin Derived Peptide-2 (MDP-2) 。高效液相色谱以及质谱检测结果表明，合成是成功的。抗菌谱研究表明，MDP-1和MDP-2 对革兰氏阳性菌、阴性菌以及真菌均具有明显的抑制作用，同时，合成的MDP由于序列短且有两对二硫键，因此对于温度及人血浆均表现出很强的稳定性。上述研究结果为深入了解厚壳贻贝抗菌肽Mytilin的抗菌机制以及在此基础上开发具有应用价值的新型抗菌肽奠定了基础。

Abstract:

As a key role in mussel defense system, Mytilin is an important antibacterial peptide isolated from the mussel serum. The structural and functional researches on Mytilin showed that the fragment connecting two β-sheets in a stable β-hairpin structure was probably required for antimicrobial activity. To elucidate the structural features and the antimicrobial activity of this fragment, we re-designed and synthesized two peptides corresponding to the main mimic structures of Mytilin-1 from Mytilus coruscus, we named these two peptides Mytilin Derived Peptide-1 and Mytilin Derived Peptide-2, respectively. Using a liquid growth inhibition assay, we evaluated their activity towards Gram-positive, Gram-negative bacteria and fungus. The results showed that both peptides can inhibit the growth of Gram-positive, Gram-negative bacteria and fungus. Besides, these two peptides showed high stability in heat water and human serum. These works laid the foundation for further research on the molecular mechanism of Mytilin and for further exploitation of antibacterial peptides with lower molecular mass and more stable structure.