青环海蛇cathelicidins家族抗菌肽Hc-CATH的构效关系研究

Cathelicidins是脊椎动物体内一个重要的抗菌肽家族，其成员是设计新型多肽类抗微生物药物的优良模板。但由于许多具有一定的溶血活性，限制了它们直接的开发应用。我们前期从青环海蛇（Hydrophis cyanocinctus Daudin）毒腺cDNA文库中克隆到一条cathelicidins家族抗菌肽基因。该基因编码的成熟肽Hc-CATH与已知cathelicidins家族抗菌肽氨基酸序列差异显著，但同样具有广谱高效的抗微生物活性和一定的溶血活性。本项目拟在前期工作基础上，对Hc-CATH的功能、高级结构和抗微生物机理进行深入研究，在此基础上对Hc-CATH进行分子改造,并对改造多肽的功能进行研究，找到影响Hc-CATH抗微生物活性和溶血活性的关键氨基酸残基位点，为其进一步的定向改造研究奠定基础，并为新型多肽类抗微生物药物的设计和改造提供分子模板和理论支持。

Cathelicidins are a family of important antimicrobial peptides in vertebrates. They are excellent templates for the design of novel peptide anti-microbial agents. However, some of them possess certain hemolytic activity, which limit their direct application. Previously, we cloned a cathelicidin gene encoding Hc-CATH from the venomous gland cDNA library of Hydrophis cyanocinctus Daudin. There is significant sequence difference between Hc-CATH and other cathelicidins. However, like other cathelicidins, Hc-CATH possesses strong and broad-spectrum antimicrobial activity and certain hemolytic activity. Based on the preliminary work, the fuction, structure and antimicrobial mechanism of Hc-CATH will be deeply studied. On this basis, molecular modification study of Hc-CATH will be carried out and the functions of modified peptides will be examined. Aim of the present project is to find the key amino acid residues which are important for Hc-CATH to maintain its antimicrobial and hemolytic activity, construct basis for its subsquent directional modification study and provide templates and theoretical support for the design of novel peptide anti-microbial agents.