Structure-Activity Relationships for Enzyme-ChaoKosmotropic Polymer Conjugates

Research Group

Karina L. Hollenkamp

Ezekiel N. Stephen

Dr. Rock J. Mancini

Introduction

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Research Group

Department of Chemistry and Biochemistry, Miami University

Picture of a young woman with blonde hair smiling and sitting at a table in a restaurant. There are windows in the background showing mountains and forest outside.

Karina L. Hollenkamp

Undergraduate presenter.

Biochemistry (B.S.) and Premedical Studies

hollenkl@miamioh.edu

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Ezekiel N. Stephen

Graduate researcher and mentor.

Doctoral candidate in chemistry.

stepheen@miamioh.edu

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Dr. Rock J. Mancini

Faculty researcher and mentor.

Assistant Professor

mancinr@miamioh.edu

Introduction

Many pharmaceuticals require specific storage conditions to work properly and effectively. Proteins and enzymes are particularly susceptible to degradation during transport or storage due to temperature fluctuation [1]. Kosmotropic protein conjugates, such as trehalose glycopolymers, are agents that stabilize the structure of water and have been shown to protect proteins against harsh environmental conditions, such as extreme temperatures [1,2]. Another area of interest is the enhancement of drug activity. The addition of chaotropic protein conjugates (agents that disrupt the structure of water), such as polymerized NIPAM (pNIPAM), could increase enzymatic activity by slightly deforming the native conformation to one that’s more stable at higher temperatures [2,3]. Future protein conjugates would ideally provide both protection against harsh conditions and activity enhancement. A copolymer conjugate consisting of trehalose glycopolymer and pNIPAM that has both kosmotropic and chaotropic effects is hypothesized to provide both protection and enhancement to enzymes when subjected to extreme temperatures.

Flow chart of overall research project. Shows when alkaline phosphatase (AP) is subjected to extreme temperatures, it denatures. When AP is combined with different polymers, it can increase and/or protect enzymatic activity.

Figure 1

Alkaline phosphatase (AP) denatures at temperatures too far above or below its biological temp. (37℃ ). Incubating AP with polymer conjugates can increase activity and/or protect the enzyme from denaturing. Images made using BioRender.com.

Blue circle with enzyme inside denoting negative change in structure entropy. Red cone to the right overlapping blue circle, where the enzyme's active site is, denoting positive change in structure entropy.

Figure 2

Kosmotropic agents (blue) stabilize the structure of water and biomolecules, such as proteins, resulting in the protection of the enzyme and a net negative change in entropy [2]. Chaotropic agents (red) disrupt the structure of water. In the case of enzymes, chaotropes disrupt the native conformation making the active site more flexible and receptive, therefore increasing enzymatic activity and resulting in a net positive change in entropy [3]. A “frustrated” chaokosmotropic polymer may be made possible if the chaotropic and kosmotropic regions are sterically hindered (big) enough to prevent neutralizing effects. Image made using BioRender.com.

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