8-nitroguanosine-3--5--cyclic-monophosphate and Kidney-Failure--Chronic

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.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Binding, Competitive; Case-Control Studies; Chemistry, Pharmaceutical; Circular Dichroism; Cyclic GMP; Cysteine; Dose-Response Relationship, Drug; Drug Design; Enzyme-Linked Immunosorbent Assay; Escherichia coli; Female; Humans; Japan; Kidney Failure, Chronic; Ligands; Male; Microbial Sensitivity Tests; Middle Aged; Protein Binding; Protein Processing, Post-Translational; Renal Dialysis; Serum Albumin; Serum Albumin, Human; Spectrometry, Fluorescence; Technology, Pharmaceutical