Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors
文献类型：期刊论文
| 作者 | Gulyas, Kinga Virag1,11; Zhou, Liping10; Salamonsen, Daniel9; Prester, Andreas8; Bartels, Kim8; Bosman, Robert8; Haffke, Paul8; Li, Jintian10; Tamasi, Viola7; Deufel, Fritz1,11 |
| 刊名 | COMMUNICATIONS CHEMISTRY
 |
| 出版日期 | 2025-04-19 |
| 卷号 | 8期号:1页码:13 |
| ISSN号 | 2399-3669 |
| DOI | 10.1038/s42004-025-01510-5 |
| 通讯作者 | Erdelyi, Mate(mate.erdelyi@kemi.uu.se) |
| 英文摘要 | Antibiotic resistance is a growing global health threat that risks the lives of millions. Among the resistance mechanisms, that mediated by metallo-beta-lactamases is of particular concern as these bacterial enzymes dismantle most beta-lactam antibiotics, which are our widest applied and cheapest to produce antibiotic agents. So far, no clinically applicable metallo-beta-lactamase inhibitors are available. Aiming to adapt to structural variations, we introduce the inhibitor concept: dynamically chiral phosphonic acids. We demonstrate that they are straightforward to synthesize, penetrate bacterial membranes, inhibit the metallo-beta-lactamase enzymes NDM-1, VIM-2 and GIM-1, and are non-toxic to human cells. Mimicking the transition state of beta-lactam hydrolysis, they target the Zn ions of the metallo-beta-lactamase active site. As a unique feature, both of their stereoisomers bind metallo-beta-lactamases, which provides them unparalleled adaptability to the structural diversity of these enzymes, and may allow them to hamper bacteria's ability for resistance development. |
| WOS关键词 | CATION-PI INTERACTIONS ; BINDING ; MECHANISM ; ANALOG ; VIM-2 ; ROLES ; ZINC |
| 资助项目 | Department of Chemistry-BMC ; Disciplinary Domain of Medicine and Pharmacy, Uppsala University ; Swedish National Infrastructure for Computing (SNIC) through National Supercomputer Center (NSC)[NAISS 2023/5-392] ; Swedish National Infrastructure for Computing (SNIC) through National Supercomputer Center (NSC)[2024/5-583] ; Swedish Research Council[2013-8804] ; Swedish Research Council[2024-05496] ; NSFC-STINT[82211530060] ; Uppsala Antibiotic Center ; Swedish Society for Medical Research[PD20-0191] ; Ake Wiberg Foundation[M22-0199] ; Max Planck Society ; DFG[458246365] ; Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund ; Federal Ministry of Education and Research, Germany[01KI2114] ; TKP2021-EGA funding scheme ; [TKP2021-EGA-24] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001471182500001 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317449]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Erdelyi, Mate |
| 作者单位 | 1.Uppsala Univ, BMC, Dept Chem, Organ Chem, Uppsala, Sweden 2.Uppsala Univ, Ctr Excellence Chem Mech Life, Uppsala, Sweden 3.Univ Hamburg, Inst Nanostruct & Solid State Phys, Hamburg, Germany 4.Max Planck Inst Struct & Dynam Matter, Hamburg, Germany 5.Lund Prot Prod Platform, Lund, Sweden 6.Univ Gothenburg, Ctr Antibiot Resistance Res, CARe, Dept Chem & Mol Biol, Gothenburg, Sweden 7.Semmelwe Univ, Dept Mol Biol, Budapest, Hungary 8.Univ Med Ctr Hamburg Eppendorf UKE, Hamburg, Germany 9.UiT Arctic Univ Norway, Fac Sci & Technol, Dept Chem, Tromso, Norway 10.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gulyas, Kinga Virag,Zhou, Liping,Salamonsen, Daniel,et al. Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors[J]. COMMUNICATIONS CHEMISTRY,2025,8(1):13. |
| APA | Gulyas, Kinga Virag.,Zhou, Liping.,Salamonsen, Daniel.,Prester, Andreas.,Bartels, Kim.,...&Erdelyi, Mate.(2025).Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors.COMMUNICATIONS CHEMISTRY,8(1),13. |
| MLA | Gulyas, Kinga Virag,et al."Dynamically chiral phosphonic acid-type metallo-β-lactamase inhibitors".COMMUNICATIONS CHEMISTRY 8.1(2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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