A novel synthetic method for backbone-cyclized polypeptide POL7080 with the help of hydrophobic-support materials.
Xiaotong GuWeijin ChenTing GuoXiaohong ChangShenyan ZhangBingfang BaiShutao MaPublished in: Organic & biomolecular chemistry (2023)
Murepavadin (POL7080) in phase III clinical trials, a backbone-cyclized polypeptide composed of 14 amino acids, has a novel mode of action and shows a specific and efficient bactericidal effect against multidrug-resistant Pseudomonas aeruginosa . It is a potential candidate to treat severe P. aeruginosa infections in the future and still has significant commercial value for further research and development. In this paper, we report a liquid-phase peptide synthetic route for this valuable candidate polypeptide assisted by hydrophobic-support materials (tags), which overcomes the difficulties of high cost and poor yield in the traditional solid-phase synthesis of macrocyclic peptides. Through the careful optimization of reaction conditions and the innovative strategy of synthetic post-treatment, we established a simple and efficient liquid-phase synthetic route suitable for POL7080 and other similar structures, with satisfactory yield, high purity and a production process not being controlled by scale.
Keyphrases
- phase iii
- clinical trial
- ionic liquid
- multidrug resistant
- pseudomonas aeruginosa
- amino acid
- open label
- acinetobacter baumannii
- drug resistant
- cystic fibrosis
- phase ii
- gram negative
- current status
- early onset
- randomized controlled trial
- mass spectrometry
- staphylococcus aureus
- double blind
- biofilm formation
- climate change
- replacement therapy
- electron transfer
- combination therapy