Characterization of tolazamide binding with glycated and normal human serum albumin by using high-performance affinity chromatography

Pingyang Tao, Zhao Li, Ashley G. Woolfork, David S. Hage

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Sulfonylurea drugs are antidiabetic drugs that are utilized in the treatment of type II diabetes and often have significant binding with human serum albumin (HSA). Immobilized samples of normal or glycated HSA in affinity microcolumns were used to investigate interactions of these proteins with the sulfonylurea drug tolazamide. HPLC and frontal analysis were used to first examine the overall binding of this drug with these samples of HSA. It was found that tolazamide had two general classes of binding sites (i.e., high and low affinity) for normal and glycated HSA. The higher affinity sites had binding constants of around 4.3–6.0 × 10 4 M −1 for these interactions at pH 7.4 and 37 °C, while the lower affinity sites had binding strengths of 4.9–9.1 × 10 3 M −1 . Zonal competition studies between tolazamide and probes for Sudlow sites I and II on HSA were also performed and used to provide site-specific affinities for tolazamide at these sites. A decrease of 22% in affinity was observed for tolazamide at Sudlow site I and an increase up to 58% was seen at Sudlow site II when comparing glycated HSA with normal HSA. These observed changes were compared to those of other first-generation sulfonylurea drugs, providing information on how glycation can alter the total and local binding strength of tolazamide and related compounds with HSA under levels of glycation seen in patients with diabetes.

Original languageEnglish (US)
Pages (from-to)273-280
Number of pages8
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume166
DOIs
StatePublished - Mar 20 2019

Keywords

  • Affinity microcolumn
  • Drug-protein binding
  • Glycation
  • Human serum albumin
  • Tolazamide

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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