Chromatographic studies of chlorpropamide interactions with normal and glycated human serum albumin based on affinity microcolumns
Autor: | Zhao Li, Pingyang Tao, David S. Hage, Ryan Matsuda |
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Rok vydání: | 2018 |
Předmět: |
Glycation End Products
Advanced 0301 basic medicine Chlorpropamide Drug medicine.drug_class media_common.quotation_subject Clinical Biochemistry Serum Albumin Human Plasma protein binding 01 natural sciences Biochemistry Chromatography Affinity Article Analytical Chemistry 03 medical and health sciences Affinity chromatography Glycation medicine Humans Glycated Serum Albumin Serum Albumin media_common Chromatography Chemistry Elution 010401 analytical chemistry Cell Biology General Medicine Human serum albumin Sulfonylurea 0104 chemical sciences body regions 030104 developmental biology embryonic structures Protein Binding medicine.drug |
Zdroj: | Journal of Chromatography B. :64-73 |
ISSN: | 1570-0232 |
Popis: | Sulfonylurea drugs have significant binding to proteins in blood, with most of this binding believed to occur with human serum albumin (HSA). High performance affinity chromatography and affinity microcolumns containing immobilized HSA were used to investigate binding by the sulfonylurea drug chlorpropamide to normal HSA and glycated HSA, which is a modified form of HSA that has an increased serum concentration in diabetes. Experiments employing frontal analysis indicated that the binding by chlorpropamide gave a good fit to a two-site model for both normal HSA and glycated HSA samples that were representative of controlled or advanced diabetes. These interactions involved a set of moderate-to-high affinity sites and a set of lower affinity sites, with binding constants in the range of 6.2–9.9 × 104 M−1 and 0.18–0.57 × 104 M−1, respectively, at pH 7.4 and 37 °C. Competition studies utilizing a zonal elution format demonstrated that chlorpropamide could interact at both Sudlow sites I and II of HSA, with affinities in the range expected for the moderate-to-high affinity sites of this drug. The affinity of chlorpropamide at Sudlow site I had a small increase of up to 1.2-fold when comparing the normal HSA and glycated HSA samples. Chlorpropamide gave a larger 1.4- to over 1.5-fold increase at Sudlow site II when the affinity of this drug was compared between normal HSA and the same samples of glycated HSA. These results were compared to those obtained previously with other sulfonylurea drugs to help determine how glycation can change the overall and site-selective binding strength of these drugs with HSA at levels of protein modification that are seen in patients with diabetes. |
Databáze: | OpenAIRE |
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