Details

Autor(en) / Beteiligte

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

Titel

S-Guanylation of Human Serum Albumin is a Unique Posttranslational Modification and Results in a Novel Class of Antibacterial Agents

Ist Teil von

• Journal of pharmaceutical sciences, 2012-09, Vol.101 (9), p.3222-3229

Ort / Verlag

Hoboken: Elsevier Inc

Erscheinungsjahr

2012

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association.