S-guanylation of human serum albumin is a unique posttranslational modification and results in a novel class of antibacterial agents

Authors

  • Yu Ishima,

    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
    2. Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
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  • Hitomi Hoshino,

    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
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  • Takuya Shinagawa,

    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
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  • Kaori Watanabe,

    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
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  • Takaaki Akaike,

    1. Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
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  • Tomohiro Sawa,

    1. Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
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  • Ulrich Kragh-hansen,

    1. Department of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark
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  • Toshiya Kai,

    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
    2. Tohoku Nipro Pharmaceutical Corporation, Fukushima 969-0401, Japan
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  • Hiroshi Watanabe,

    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
    2. Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
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  • Toru Maruyama,

    Corresponding author
    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
    2. Center for Clinical Pharmaceutical Science, Kumamoto University, Kumamoto, Japan
    • Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan. Telephone: +81-96-326-3887; Fax: +81-96-326-5048
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  • Masaki Otagiri

    Corresponding author
    1. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
    2. Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan
    3. DDS Research Institute, Sojo University, Kumamoto 860-0082, Japan
    • Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan. Telephone: +81-96-371-4150; Fax: +81-96-362-7690
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Abstract

8-Nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) is a nitric oxide metabolite and an important second messenger. 8-Nitro-cGMP reacts with sulfhydryl groups forming a novel posttranslational modification, namely, S-guanylation. In this work, we found, by using a quantitative competition enzyme-linked immunosorbent assay procedure, that S-guanylated human serum albumin (S-cGMP-HSA) is a component of normal plasma, and that hemodialysis patients decrease its concentration, on an average, from 68 to 34 nM. End-stage renal disease is often accompanied by septicemia, and we found that S-cGMP-HSA possesses an in vitro antibacterial effect with half maximal inhibitory concentration of approximately 2 μM against Escherichia coli American Type Culture Collection. Our findings indicate that S-cGMP-HSA can be regarded as an endogenous antibacterial agent in healthy conditions and as a useful new class of antibacterial agents with a circulation time sufficient for in vivo biological activity. The clinical development of S-cGMP-HSA as a safe and strong antibacterial agent arisen from endogenous posttranslational modification would be expected. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3222–3229, 2012

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