Physical Sciences and Mathematics Commons^™

Analysis Of Drug-Protein Interactions During Diabetes By High-Performance Affinity Chromatography, Pingyang Tao

Department of Chemistry: Dissertations, Theses, and Student Research

High-performance affinity chromatography (HPAC) is a type of liquid chromatography in which solutes are separated based on their binding to a stationary phase that is a biologically-related agent. Sulfonylurea drugs have significant binding to proteins in blood, with most of this binding is believed to occur with human serum albumin (HSA). HSA is known to be modified as a result of the high serum levels of glucose that is present during diabetes, which may also alter the function of HSA as a binding agent for many drugs in circulation. Some modifications of HSA that can occur during diabetes involves early …

Chromatographic Analysis Of Drug-Protein Interactions During Diabetes And Characterization Of Human Serum Albumin Through Multidimensional Mass Spectrometry, Ryan E. Matsuda

Department of Chemistry: Dissertations, Theses, and Student Research

Diabetes is a metabolic disease that can lead to the non-enzymatic glycation of serum proteins such as human serum albumin (HSA). Previous studies have indicated that glycation can affect the structure and function of these proteins. This dissertation describes the development of tools and techniques based on high performance affinity chromatography (HPAC) and multidimensional mass spectrometry to analyze the effects of glycation on the function and structure of HSA.

A major portion of this research involved the utilization of HPAC to examine the effect of glycation on the binding of three second-generation sulfonylurea drugs and one third-generation sulfonylurea drug. These …

Chromatographic Studies Of Drug-Protein Binding In Diabetes, Kathryn (Krina) S. Joseph

Department of Chemistry: Dissertations, Theses, and Student Research

Drug-protein binding can have a dramatic impact on the distribution and metabolism of a drug. This manuscript describes the use of high-performance affinity chromatography to examine the binding of various compounds to human serum albumin (HSA) in normal and diabetic disease states.

The first study examined the use of four coumarin compounds as possible alternatives to warfarin as a probe for Sudlow site I on HSA. High-performance affinity chromatography and immobilized HSA columns were used to compare and evaluate the binding properties of these probe candidates. It was found from this group that 4-hydroxycoumarin was the best alternative to warfarin …