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Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors
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Yue LI1, Guo-qing LI2, Yuan-yuan TIAN3, Cong-ran LI2, Xin-yi YANG2, *, Kai-hu YAO1, *, Xue-fu YOU2, *
Acta Pharmaceutica Sinica | 2024, 59(2) : 279 - 288
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Acta Pharmaceutica Sinica | 2024, 59(2): 279-288
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Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors
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Yue LI1, Guo-qing LI2, Yuan-yuan TIAN3, Cong-ran LI2, Xin-yi YANG2, *, Kai-hu YAO1, *, Xue-fu YOU2, *
Affiliations
  • 1. National Center for Children's Health/Beijing Children's Hospital, Capital Medical University/Beijing Pediatric Research Institute/National Clinical Research Center for Respiratory Diseases/Key Laboratory of Major Diseases in Children, Ministry of Education/Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing 100045, China
  • 2. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
  • 3. Department of Dermatology, National Center for Children's Health/Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
Published: 2024-02-12 doi: 10.16438/j.0513-4870.2023-0903
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The outer membrane composed predominantly of lipopolysaccharide (LPS) is an essential biological barrier for most Gram-negative (G-) bacteria. Lipopolysaccharide transport protein (Lpt) complex LptDE is responsible for the critical final stage of LPS transport and outer membrane assembly. The structure and function of LptDE are highly conserved in most G- bacteria but absent in mammalian cells, and thus LptDE complex is regarded as an attractive antibacterial target. In recent 10 years, the deciphering of the three-dimensional structure of LptDE protein facilities the drug discovery based on such "non-enzyme" proteins. Murepavadin, a peptidomimetic compound, was reported to be the first compound able to target LptD, enlightening a new class of antibacterial molecules with novel mechanisms of action. This article is devoted to summarize the molecular characteristics, structure-function of LptDE protein complex and review the development of murepavadin and related peptidomimetic compounds, in order to provide references for relevant researches.

Gram-negative bacteria  /  lipopolysaccharide outer membrane  /  lipopolysaccharide transport protein complex DE  /  new antibacterial drug target  /  novel peptidomimetic compound
Yue LI, Guo-qing LI, Yuan-yuan TIAN, Cong-ran LI, Xin-yi YANG, Kai-hu YAO, Xue-fu YOU. Novel antibacterial drug target against Gram-negative bacteria: lipopolysaccharide transport protein LptDE and its inhibitors[J]. Acta Pharmaceutica Sinica, 2024 , 59 (2) : 279 -288 . DOI: 10.16438/j.0513-4870.2023-0903
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Article Info
doi: 10.16438/j.0513-4870.2023-0903
  • Receive Date：2023-07-25
  • Online Date：2025-11-28
  • Published：2024-02-12
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History
  • Received：2023-07-25
  • Revised：2023-09-14
Funding
Affiliations
    1. National Center for Children's Health/Beijing Children's Hospital, Capital Medical University/Beijing Pediatric Research Institute/National Clinical Research Center for Respiratory Diseases/Key Laboratory of Major Diseases in Children, Ministry of Education/Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Beijing 100045, China
    2. Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
    3. Department of Dermatology, National Center for Children's Health/Beijing Children's Hospital, Capital Medical University, Beijing 100045, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
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Genus		 种数
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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