Serum albumins are an important class of proteins that are found nearly ubiquitously across the animal kingdom and have been found in various forms in plants.  In mammals, albumins are critical participants in the maintenance of oncotic blood pressure and also function as transport proteins of fatty acids, transition metals, inorganic ions, and organic molecules including vitamins, metabolites, toxins, and drugs.  In this capacity albumin proteins are important for regulating so-called absorption, distribution, metabolism, and elimination (ADME) aspects of drug delivery.  Human serum albumin has been shown to be important for buffering the free serum concentrations of the anti-coagulant warfarin.  Recent efforts in our laboratory to measure the energetic basis of molecular recognition of substituted warfarins by serum albumins has revealed an intriguing observation.  In the presence of various buffer salt,s which have previously been assumed to be necessary for protein stability, serum albumin actually is rendered more unstable and prone to aggregation than in solutions with no added buffers at physiological concentrations.  Here we present thermal analytical data which reveal this unexpected destabilization and aggregation behavior in an attempt to better understand this important protein that plays such a critical role in maintaining mammalian physiology.  Results are presented in the context of drug-binding studies of substituted warfarins.

Differential scanning calorimetry studies reveal the curious influence of buffer salts on the stability and aggregation of serum albumin

255th National Meeting (2018)

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