title: S-guanylation of human serum albumin is a unique posttranslational modification and results in a novel class of antibacterial agents.
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.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ishima
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hoshino
authors.forename: Takuya
authors.initials: T
authors.lastname: Shinagawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Watanabe
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sawa
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kragh-Hansen
authors.forename: Toshiya
authors.initials: T
authors.lastname: Kai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000378:metabolism*; D001667:Binding, Competitive; D016022:Case-Control Studies; D002626:Chemistry, Pharmaceutical; D002942:Circular Dichroism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D003545:Cysteine; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D005260:Female; D006801:Humans; D007564:Japan; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D008024:Ligands; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism*; D000075462:Serum Albumin, Human; D013050:Spectrometry, Fluorescence; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: C525106:8-nitroguanosine 3',5'-cyclic monophosphate; C422455:ALB protein, human; D000900:Anti-Bacterial Agents; D008024:Ligands; D012709:Serum Albumin; D006152:Cyclic GMP; D003545:Cysteine; D000075462:Serum Albumin, Human