高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

[杨石先生诞辰130周年纪念专辑]兼具抗革兰氏阳性与阴性菌活性的多黏菌素类似物的开发

马文洁1，张冰3，汪嘉琪2，Blasco Pilar2，高鹏4，徐剑超5，陈声3，李学臣1,2   

  1. 1. 中国科学院上海有机化学研究所，沪港化学合成联合实验室 2. 香港大学化学系，合成化学国家重点实验室 3. 香港理工大学食品科学与营养学系，化学生物学及药物发现国家重点实验室 4. 香港大学牙医学院应用口腔科学及社区牙科护理系 5. 苏州耐科泰生物科技有限公司
  • 收稿日期:2026-05-24 修回日期:2026-06-17 出版日期:2026-06-21 发布日期:2026-06-21
  • 通讯作者: 李学臣 E-mail:xuechenl@hku.hk
  • 基金资助:
    国家自然科学基金(批准号: 22507135)和香港研究资助局项目(批准号: JLFS/P-404/24)资助

Development of Polymyxin Analogs with Expanded Activity Against Both Gram-Positive and Gram-Negative Bacteria

MA Wenjie1*, ZHANG Bing3, WANG Jiaqi2, BLASCO Pilar2, GAO Peng4, XU Jianchao5, CHEN Sheng3*, LI Xuechen1,2*   

  1. 1. Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences 2. State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong 3. State Key Laboratory of Chemical Biology and Drug Discovery, Department of Food Science and Nutrition, The Hong Kong Polytechnic University 4. Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong 5. Suzhou NexTide Co., Ltd.
  • Received:2026-05-24 Revised:2026-06-17 Online:2026-06-21 Published:2026-06-21
  • Supported by:
    Supported by the National Natural Science Foundation of China(No. 22507135) and the Research Grants Council of Hong Kong(No. JLFS/P-404/24)

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摘要： 日益严峻的细菌感染威胁使得新型抗生素的研发迫在眉睫.本文报道了一种新型多黏菌素类似物PL-082，其N端脂肪链和首个氨基酸经过了结构改造.与仅抗革兰氏阴性菌的传统多黏菌素不同，PL-082展现出对革兰氏阳性菌和阴性菌均有效的广谱抗菌活性.通过核磁共振（NMR）和分子动力学模拟，我们揭示了PL-082与POPG磷脂（革兰氏阳性菌细胞膜的主要成分）之间的强相互作用，这正是其获得抗革兰氏阳性菌独特活性的分子机制.本研究不仅阐明了新抗生素PL-082的抗菌机制，更为开发强效广谱抗生素提供了新思路.

关键词: 多黏菌素类似物, 革兰氏阳性菌, POPG磷脂

Abstract: The increasing threat of bacterial infections has created an urgent need for novel antibiotics. Herein, we report a novel polymyxin analog, PL-082, modified at its N-terminal lipid and first amino acid. Distinct from conventional polymyxins, which are exclusively active against Gram-negative bacteria, PL-082 exhibits expanded antibacterial activity against both Gram-positive and Gram-negative bacteria. Through NMR and molecular dynamics simulations, we reveal that the strong interactions between PL-082 and POPG phospholipids—a dominant component of Gram-positive bacterial membrane—account for its unique activity against Gram-positive bacteria. Beyond elucidating the antibacterial mechanism of the novel antibiotic PL-082, this work also provides promising avenues for the development of potent, broad-spectrum antibiotics.

Key words: Polymyxin analog, Gram-positive bacteria, POPG phospholipids

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