کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1201863 1493660 2012 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Analysis of drug interactions with modified proteins by high-performance affinity chromatography: Binding of glibenclamide to normal and glycated human serum albumin
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Analysis of drug interactions with modified proteins by high-performance affinity chromatography: Binding of glibenclamide to normal and glycated human serum albumin
چکیده انگلیسی

High-performance affinity chromatography (HPAC) was used to examine the changes in binding that occur for the sulfonylurea drug glibenclamide with human serum albumin (HSA) at various stages of glycation for HSA. Frontal analysis on columns containing normal HSA or glycated HSA indicated glibenclamide was interacting through both high affinity sites (association equilibrium constant, Ka, 1.4–1.9 × 106 M−1 at pH 7.4 and 37 °C) and lower affinity sites (Ka, 4.4–7.2 × 104 M−1). Competition studies were used to examine the effect of glycation at specific binding sites of HSA. An increase in affinity of 1.7- to 1.9-fold was seen at Sudlow site I with moderate to high levels of glycation. An even larger increase of 4.3- to 6.0-fold in affinity was noted at Sudlow site II for all of the tested samples of glycated HSA. A slight decrease in affinity may have occurred at the digitoxin site, but this change was not significant for any individual glycated HSA sample. These results illustrate how HPAC can be used as tool for examining the interactions of relatively non-polar drugs like glibenclamide with modified proteins and should lead to a more complete understanding of how glycation can alter the binding of drugs in blood.


► HPLC affinity columns were used to study drug binding with modified proteins.
► Binding of glibenclamide with glycated human serum albumin (HSA) was studied.
► Frontal analysis was used to detect global changes in binding for glycated HSA.
► Competition studies examined site-specific changes in binding by glibenclamide.
► Local changes in binding upon HSA glycation were seen at Sudlow sites I and II.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography A - Volume 1265, 23 November 2012, Pages 114–122
نویسندگان
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