TAG-Assisted Liquid-Phase Synthesis and Structure Activity Relationship of Macolacin-Based Side-to-Tail Cyclopeptides Antibiotic
Haidi Li
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
These authors contributed equally to this work.
Search for more papers by this authorYuankui Jin
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
These authors contributed equally to this work.
Search for more papers by this authorMinfan Pei
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorLinyan Zhang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorLianjun Wang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorYuxin Yang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorPeng Xiang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorCorresponding Author
Taigang Liang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
E-mail: [email protected]Search for more papers by this authorHaidi Li
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
These authors contributed equally to this work.
Search for more papers by this authorYuankui Jin
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
These authors contributed equally to this work.
Search for more papers by this authorMinfan Pei
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorLinyan Zhang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorLianjun Wang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorYuxin Yang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorPeng Xiang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Search for more papers by this authorCorresponding Author
Taigang Liang
Shanxi Provincial Key Laboratory of Drug Synthesis and Novel Pharmaceutical Preparation Technology, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, 030001 China
E-mail: [email protected]Search for more papers by this authorComprehensive Summary
TAG-assisted peptide synthesis technology enables optimal conservation of Fmoc amino acid raw materials and chemical solvents while eliminating the need for intricate chromatographic purification processes. This work presents a 4,4'-diphenylphosphonoxy diphenylcarbinol tag-mediated liquid-phase synthesis approach for preparing side-to-tail cyclopeptides macolacin which has strong activity against gram-negative bacteria, and its 15 analogues containing four N-methylation modified cyclopeptides, as well as an investigation of their structure-activity relationship (SAR). The synthesis of macolacin analogues primarily focuses on the modifications of the N-methylation group of Ile-7 and the tail fatty acyl chain of macolacin. The incorporation of N-methylation for Ile-7, along with the dihalogenated or monohalogenated benzoic acids for tail modification, exhibited remarkable antibacterial efficacy and minimal hepatocellular toxicity in vitro. The present study identified an N-methylation-modified antimicrobial cyclopeptide Ma14 that exhibits rapid bactericidal efficacy against A. baumanii, etc., while showing reduced hepatocellular toxicity. Molecular docking simulations were conducted to investigate the binding of cyclopeptides to the outer membrane protein BamA of A. baumannii. The findings demonstrated the stable binding interactions of the cyclopeptides with the BamA protein and then presented a novel approach to explain the bacteriostatic mechanism of macolacin-based cyclopeptide antibiotics.
Supporting Information
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Appendix S1: Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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