title: Modulation of the thermodynamic stability of proteins by polyols: significance of polyol hydrophobicity and impact on the chemical potential of water.
abstract: The exact mechanism of the modulation of chemical potential of proteins by polyols is not yet well understood. Present study investigates the role of hydrophobicity of polyols, and their impact on water activity and/or surface tension, in determining their stabilization/destabilization potential. Results with ribose and methyl-glucose show that the enhanced stability of proteins is not mediated via the effect on interfacial tension, a hypothesis that has so far been restricted to glycerol. An exemplary correlation between thermodynamic stabilization (ΔG(f-uf)), and polyol osmolality, confirms/generalizes the prominent role of water activity in the observed stabilization effects. Results show that even seemingly hydrophilic sugars such as deoxy-ribose can interact favorably with proteins, suggesting that properties other than the presence of hydroxyl groups also contribute to the net effect of polyols. We demonstrate that the hydrophobicity index of polyols and the net stabilization effect afforded to proteins have an excellent inverse correlation. These studies show that the weak hydrophobicity of polyols is critical for promoting their interactions with proteins, weakening of the hydrophobic forces within the protein interior and counteracting the polyol induced-solvent mediated stabilization effect.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States.
authors.forename: Vineet
authors.initials: V
authors.lastname: Kumar
authors.forename: Ravi
authors.initials: R
authors.lastname: Chari
authors.forename: Vikas K
authors.initials: VK
authors.lastname: Sharma
authors.forename: Devendra S
authors.initials: DS
authors.lastname: Kalonia
mesh_terms: D002241:Carbohydrates / Q000737:chemistry; D016207:Cytokines / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D016898:Interferon-alpha / Q000737:chemistry; D009994:Osmolar Concentration; D011108:Polymers / Q000737:chemistry*; D055550:Protein Stability / Q000187:drug effects; D011506:Proteins / Q000737:chemistry; D012995:Solubility; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D016207:Cytokines; D005079:Excipients; D016898:Interferon-alpha; D011108:Polymers; D011506:Proteins; D013501:Surface-Active Agents; C024617:polyol; D014867:Water; D005990:Glycerol