1. S-guanylation of human serum albumin is a unique posttranslational modification and results in a novel class of antibacterial agents.
- Author
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Ishima Y, Hoshino H, Shinagawa T, Watanabe K, Akaike T, Sawa T, Kragh-Hansen U, Kai T, Watanabe H, Maruyama T, and Otagiri M
- Subjects
- Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents blood, Binding, Competitive, Case-Control Studies, Chemistry, Pharmaceutical, Circular Dichroism, Cyclic GMP blood, Cyclic GMP metabolism, Cysteine, Dose-Response Relationship, Drug, Drug Design, Enzyme-Linked Immunosorbent Assay, Escherichia coli growth & development, Female, Humans, Japan, Kidney Failure, Chronic therapy, Ligands, Male, Microbial Sensitivity Tests, Middle Aged, Protein Binding, Renal Dialysis, Serum Albumin, Human, Spectrometry, Fluorescence, Technology, Pharmaceutical methods, Anti-Bacterial Agents metabolism, Cyclic GMP analogs & derivatives, Escherichia coli drug effects, Kidney Failure, Chronic blood, Protein Processing, Post-Translational, Serum Albumin metabolism
- 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., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
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