Chromatographic studies of chlorpropamide interactions with normal and glycated human serum albumin based on affinity microcolumns

Pingyang Tao, Zhao Li, Ryan Matsuda, David S Hage

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1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)64-73
Number of pages10
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1097-1098
DOIs
StatePublished - Oct 15 2018

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Chlorpropamide
Serum Albumin
Medical problems
Pharmaceutical Preparations
Binding Sites
Affinity chromatography
Affinity Chromatography

Keywords

  • Affinity microcolumn
  • Chlorpropamide
  • Drug-protein binding
  • Glycation
  • High-performance affinity chromatography
  • Human serum albumin

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

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title = "Chromatographic studies of chlorpropamide interactions with normal and glycated human serum albumin based on affinity microcolumns",
abstract = "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.",
keywords = "Affinity microcolumn, Chlorpropamide, Drug-protein binding, Glycation, High-performance affinity chromatography, Human serum albumin",
author = "Pingyang Tao and Zhao Li and Ryan Matsuda and Hage, {David S}",
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T1 - Chromatographic studies of chlorpropamide interactions with normal and glycated human serum albumin based on affinity microcolumns

AU - Tao, Pingyang

AU - Li, Zhao

AU - Matsuda, Ryan

AU - Hage, David S

PY - 2018/10/15

Y1 - 2018/10/15

N2 - 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.

AB - 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.

KW - Affinity microcolumn

KW - Chlorpropamide

KW - Drug-protein binding

KW - Glycation

KW - High-performance affinity chromatography

KW - Human serum albumin

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U2 - 10.1016/j.jchromb.2018.09.001

DO - 10.1016/j.jchromb.2018.09.001

M3 - Article

VL - 1097-1098

SP - 64

EP - 73

JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

SN - 1570-0232

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