Irreversible Inhibition of Metallo-β-lactamase (IMP-1) by 3-(3-Mercaptopropionylsulfanyl)propionic Acid Pentafluorophenyl Ester

Authors

  • Hiromasa Kurosaki Prof. Dr.,

    1. Department of Structure-Function Physical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan, Fax: (+81) 96-371-4314
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  • Yoshihiro Yamaguchi,

    1. Department of Structure-Function Physical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan, Fax: (+81) 96-371-4314
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  • Toshihiro Higashi,

    1. Department of Structure-Function Physical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan, Fax: (+81) 96-371-4314
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  • Kimitaka Soga,

    1. Department of Structure-Function Physical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan, Fax: (+81) 96-371-4314
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  • Satoshi Matsueda,

    1. Department of Structure-Function Physical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan, Fax: (+81) 96-371-4314
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  • Haruka Yumoto,

    1. Department of Structure-Function Physical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan, Fax: (+81) 96-371-4314
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  • Shogo Misumi Prof. Dr.,

    1. Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan
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  • Yuriko Yamagata Prof. Dr.,

    1. Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan
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  • Yoshichika Arakawa Prof. Dr. MD.,

    1. Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan
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  • Masafumi Goto Prof. Dr.

    1. Department of Structure-Function Physical Chemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan, Fax: (+81) 96-371-4314
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  • This work was supported by H15-Shinkou-9 from the Ministry of Health Labor and Welfare of Japan and by a Grant-in-Aid for Scientific Research (B) (No. 16390017) from the Japan Society for the Promotion of Science.

Abstract

original image

Widerstand ist sinnlos: Pathogene Bakterien, die Metallo-β-lactamasen produzieren, gelten wegen ihrer Resistenz gegen Antibiotika als große Gefahr. Nun wurde die Titelverbindung als irreversibler Inhibitor einer Metallo-β-lactamase (IMP-1) identifiziert. Laut den Befunden der Röntgenstrukturanalyse (siehe Bild) bindet der Inhibitor an IMP-1 unter Bildung einer kovalenten Amidbindung mit der Aminogruppe (Nζ) von Lys 224.

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