Molecular design and biophysical studies of a new class of lipid II-binding antibiotics

一类新型脂质 II 结合抗生素的分子设计和生物物理研究

• 批准号: 2247995
• 金额: --
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2247995
• 关键词: Molecular; design; biophysical; studies; new

New designs of antimicrobial peptides are urgently needed in order to combat the threat of antibiotic resistance. The complex polycyclic peptide nisin is a promising lead, as it binds selectively to lipid II (only found in bacteria) and forms nisin-lipid II pores which cause lysis of the bacterial cell membrane. However, to exploit this fully it is necessary to understand how the peptide structure and sequence influence both the molecular architecture of the pore and the kinetics of pore formation. This project will have both academic impact, through developing a chemical biology approach to a better understanding of the molecular recognition of this unique pore complex (academic), and industrial and societal impact, as it will form the basis for libraries of potent, simplified candidate peptides for screening for antimicrobial activity.

为了对抗抗生素耐药性的威胁，迫切需要新的抗微生物肽设计。复杂的多环肽乳链菌肽是一个有前途的铅，因为它选择性地结合到脂质II（只在细菌中发现），并形成乳链菌肽-脂质II孔，导致细菌细胞膜裂解。然而，为了充分利用这一点，有必要了解肽结构和序列如何影响孔的分子结构和孔形成的动力学。该项目将产生学术影响，通过开发一种化学生物学方法来更好地了解这种独特孔复合物的分子识别（学术），以及工业和社会影响，因为它将形成有效、简化的候选肽库的基础，用于筛选抗微生物活性。