结核病的治疗因耐药菌株的流行而陷入困境，亟待开发新型有效的抗结核机制药物。我们前期从NCBI中选择了几十种在各种分枝杆菌噬菌体中高度保守、氨基酸残基为10-50的候选多肽，化学合成并筛选抗结核杆菌H37Rv活性，获得一条多肽VV15，有显著的体内、外的杀灭结核杆菌活性，且VV15序列简短（15个氨基酸残基），细胞毒性、溶血活性和动物急性毒性低，具有开发新型生物抗结核药物的潜力。本课题拟在前期工作基础上，进一步探索VV15的抗结核专一性与抗耐药性结核的功能；对其抗结核杆菌分子机理进行深入研究，探明其高级结构与构效关系，探明其破坏结核杆菌细胞的完整性是否通过疏水相互作用结合到细胞膜两亲性的磷脂双分子层上，是否通过静电相互作用结合到带负电荷的细胞膜上；进一步探索VV15是否作用于结核杆菌细胞壁或毒力糖脂、核酸、荚膜等其它作用靶点。为开发新型生物类抗结核药物提供新候选和新思路。

At present, treatment of tuberculosis has fallen into dilemma because of the appearance of drug-resistant mycobacterium. And it is important to discover novel anti-mycobacterial mechanisms for drug development. In previous work, dozens of peptide candidates, which were severely conserved in different mycobacteriophages and composed of 10-50 amino acids with several net positive charges, were selected and synthesized from NCBI for anti-mycobacterium assay. One of them, VV15, showed strong anti-mycobacterial activity against H37Rv in vitro, and BCG in vivo. In addition, VV15 is composed of 15 amino acids with novel structure, low cytotoxicity, low hemolytic activity and acute toxicity against mammal. Based on the preliminary work, we plan to investigate the antimycobacterial specificity and antimycobacterial function on drug-resistant mycobacteria, molecular anti-mycobacterial mechanisms, tertiary structure and structure-funtion relationship of VV15. To explore it targets on mycobacterial membrane whether via the amphiphilic structure and electrostatic interaction or not. And the interactions of VV15 with other targets will also be explored, such as cell wall, cord factor, nucleic acid and polysaccharide capsule. Finally we will provide a novel candidate and new conception for biological anti-mycobacterial agents development.