Journal ArticleDOI
The peptide backbone plays a dominant role in protein stabilization by naturally occurring osmolytes
Yufeng Liu,D. W. Bolen +1 more
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TLDR
The side chains were found collectively to favor exposure to the osmolyte in comparison to exposure in water, and in this sense the side chains favor protein unfolding.Abstract:
Transfer free energy measurements of amino acids from water to the osmolytes, sucrose and sarcosine, were made as a function of osmolyte concentration. From these data, transfer free energies of the amino acid side chains were obtained, and the transfer free energy of the peptide backbone was determined from solubility measurements of diketopiperazine (DKP). Using static accessible surface evaluations of the native and unfolded states of ribonuclease A, solvent exposed side chain and peptide backbone areas were multiplied by their transfer free energies and summed in order to evaluate the transfer free energy of the native and unfolded states of the protein from water to the osmolyte solutions. The results reproduced the main features of the free energy profile determined for denaturation of proteins in the presence of osmolytes. The side chains were found collectively to favor exposure to the osmolyte in comparison to exposure in water, and in this sense the side chains favor protein unfolding. The major factor which opposes and overrides the side chain preference for denaturation and results in the stabilization of proteins observed in osmolytes is the highly unfavorable exposure of polypeptide backbone on unfolding. Except for urea and guanidine hydrochloride solutions, it is shown that all organic solvents (e.g., dioxane, ethanol, ethylene glycol) and solutes (osmolytes) for which transfer free energy measurements have been determined exhibit unfavorable transfer free energy of the peptide backbone.(ABSTRACT TRUNCATED AT 250 WORDS)read more
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Journal ArticleDOI
Instability, stabilization, and formulation of liquid protein pharmaceuticals.
TL;DR: The basic behavior of proteins, their instabilities, and stabilization in aqueous state in relation to the development of liquid protein pharmaceuticals is discussed.
Journal ArticleDOI
The osmophobic effect: natural selection of a thermodynamic force in protein folding.
D. W. Bolen,Ilia V. Baskakov +1 more
TL;DR: The osmophobic effect is a newly uncovered thermodynamic force in nature that complements the well-recognized hydrophobic interactions, hydrogen bonding, electrostatic and dispersion forces that drive protein folding.
Journal ArticleDOI
A molecular mechanism for osmolyte-induced protein stability
TL;DR: A quantitative solvation model is constructed in which backbone/solvent interaction energy is a function of interactant polarity, and the number of energetically equivalent ways of realizing a given interaction is afunction of interactionant surface area.
Book ChapterDOI
Control of Protein Stability and Reactions by Weakly Interacting Cosolvents: The Simplicity of the Complicated
Journal ArticleDOI
Why Is Trehalose an Exceptional Protein Stabilizer? AN ANALYSIS OF THE THERMAL STABILITY OF PROTEINS IN THE PRESENCE OF THE COMPATIBLE OSMOLYTE TREHALOSE
Jai K. Kaushik,Rajiv Bhat +1 more
TL;DR: The pH dependence data suggest that even though the charge status of a protein contributes significantly, trehalose can be expected to work as a universal stabilizer of protein conformation due to its exceptional effect on the structure and properties of solvent water compared with other sugars and polyols.
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