2. Academic Validation
  3. Novel antimicrobial peptides modified with fluorinated sulfono-γ-AA having high stability and targeting multidrug-resistant bacteria infections

Novel antimicrobial peptides modified with fluorinated sulfono-γ-AA having high stability and targeting multidrug-resistant bacteria infections

  • Eur J Med Chem. 2024 Jan 15:264:116001. doi: 10.1016/j.ejmech.2023.116001.
Xiaomin Guo 1,  Xiaokang Miao 1,  Yingying An 1,  Tiantian Yan 1,  Yue Jia 1,  Bochuan Deng 1,  Jianfeng Cai 2,  Wenle Yang 1,  Wangsheng Sun 3,  Rui Wang 4,  Junqiu Xie 5
Affiliations

Affiliations

  • 1 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, China.
  • 2 Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA.
  • 3 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, China. Electronic address: sunws@lzu.edu.cn.
  • 4 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. Electronic address: wangrui@lzu.edu.cn.
  • 5 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, China. Electronic address: xiejq@lzu.edu.cn.
PMID: 38056301 DOI: 10.1016/j.ejmech.2023.116001
Abstract

The emergence and increasing prevalence of multidrug-resistant (MDR) bacteria have posed an urgent demand for novel Antibacterial drugs. Currently, Antimicrobial Peptides (AMPs), potential novel antimicrobial agents with rare antimicrobial resistance, represent an available strategy to combat MDR Bacterial infections but suffer the limitation of Protease degradation. In this study, we developed a highly effective method for optimizing the stability of AMPs by introducing fluorinated sulfono-γ-AApeptides, and successfully synthesized novel Feleucin-K3-analogs. The results demonstrated that the incorporation of fluorinated sulfono-γ-AA into Feleucin-K3 effectively improved stability and afforded optimal Peptides, such as CF3-K11, which exhibited 8-9 times longer half-lives than Feleucin-K3. Moreover, CF3-K11 displayed potent antimicrobial activity against clinically isolated Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), excellent biosafety, low resistance propensity, and possessed powerful antimicrobial efficacy for both local skin Infection and pneumonia Infection. The optimal CF3-K11 exhibited strong therapeutic potential and offered a superior approach for treating MDR Bacterial infections.

Keywords

Anti-multidrug-resistant bacteria infections; Feleucin-K3 derived analogs; Fluorinated sulfono-γ-AA modification; High stability.

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