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

Yu Ishima, Hitomi Hoshino, Takuya Shinagawa, Kaori Watanabe, Takaaki Akaike, Tomohiro Sawa, Ulrich Kragh-hansen, Toshiya Kai, Hiroshi Watanabe, Toru Maruyama, Masaki Otagiri

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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 34nM. 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 2μM 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.

Original languageEnglish
Pages (from-to)3222-3229
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume101
Issue number9
DOIs
Publication statusPublished - 2012 Sep

Keywords

  • Albumin
  • Antibacterial activity
  • Biomaterials
  • Cysteine
  • Drug design
  • Ligand binding
  • Nanoparticles
  • Nitric oxide
  • Oxidation
  • Posttranslational modification

ASJC Scopus subject areas

  • Pharmaceutical Science

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