A rationale for the contrasting activity (towards globular proteins) of tert-butyl alcohol and trimethylamine N-oxide.
tert-Butyl alcohol, TBA, and trimethylamine N-oxide, TMAO, even though they are isosteric molecules, have contrasting activity towards globular proteins: the former destabilizes the native state, whereas the latter stabilizes it. TBA addition to water causes a density decrease and it tends to form self-aggregates; TMAO addition to water causes a density increase and it does not show any tendency to form self-aggregates. By inserting such experimental information in the framework of the statistical thermodynamic model devised to rationalize the conformational stability of globular proteins [G. Graziano, Phys. Chem. Chem. Phys., 2010, 12, 14245-14252], it emerges that: (a) TBA is a destabilizing agent because its addition to water causes a significant decrease in the magnitude of the contribution due to the solvent-excluded volume decrease associated with protein folding; (b) TMAO is a stabilizing agent because its addition to water causes a significant increase in the magnitude of the contribution due to the solvent-excluded volume decrease associated with protein folding.
Dipartimento di Scienze per la Biologia, la Geologia e l'Ambiente, Università del Sannio, Via Port'Arsa 11 - 82100, Benevento, Italy. graziano@unisannio.it
Giuseppe
G
Graziano
D008744:Methylamines / Q000737:chemistry*; D008958:Models, Molecular; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D020002:tert-Butyl Alcohol / Q000737:chemistry*
D008744:Methylamines; D011506:Proteins; D012997:Solvents; C005855:trimethyloxamine; D020002:tert-Butyl Alcohol