کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
30771 | 44502 | 2011 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Study on the interaction of tamiflu and oseltamivir carboxylate with human serum albumin Study on the interaction of tamiflu and oseltamivir carboxylate with human serum albumin](/preview/png/30771.png)
Oseltamivir phosphate (OP; tamiflu) is an antiviral pro-drug, which is hydrolyzed hepatically to the active metabolite oseltamivir carboxylate (OC). It is the first orally neuraminidase inhibitor that was used in the treatment and prophylaxis of influenza virus A and B infection. Human serum albumin (HSA) is the most abundant of the proteins in the blood plasma and is major transporter for delivering several drugs in vivo. This study was designed to examine the interaction of HSA with oseltamivir phosphate (OP) and oseltamivir carboxylate (OC) in aqueous solution at physiological conditions, using a constant protein concentration and various drug contents. FTIR, UV–Vis spectroscopic methods were used to determine the drugs binding mode, the binding constant and the effects of drug complexation on protein secondary structure.Structural analysis showed that OP and OC bind HSA via polypeptide polar groups with overall binding constants of KOP–HSA = 3.86(±1.05) × 103 M−1 and KOC–HSA = 1.5(±0.45) × 102 M−1. The alterations of protein secondary structure are attributed to a partial destabilization of HSA on drug complexation. The protein secondary structure showed no major alterations at low drugs concentrations (50 μM), whereas at higher content (1 mM), decrease of α-helix from 58% (free HSA) to 38% (OP–HSA)–48% (OC–HSA), decrease of random coil from 15% (free HSA) to 2% (OP–HSA)–3% (OC–HSA), increase of β-sheet from 6% (free HSA) to 20% (OC–HSA)–29% (OP–HSA) and turn from 8% (free HSA) to 17% (OC–HSA)–19% (OP–HSA) occurred in the drug–HSA complexes. These observations indicated that low drug content induced protein stabilization, whereas at high drug concentration, a partial protein destabilization occurred in these drug–HSA complexes.
► The binding affinity of oseltamivir phosphate and oseltamivir carboxylate to HSA was determined.
► The stronger binding was observed for oseltamivir phosphate than oseltamivir carboxylate.
► At high drug concentrations protein destabilization was observed.
► HSA is not a good transporter for oseltamivir phosphate and oseltamivir carboxylate due to a weak drug-protein interaction.
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 105, Issue 1, 5 October 2011, Pages 34–39