Noncovalent Interactions of Long-Chain Perfluoroalkyi Acids with Semm Albumin

摘要

Preferential distribution of long-chain perfluoroalkyi acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K_a) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA: albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10~6 M~(-1) with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (< 10~(-3)), corresponding to a high protein-water distribution coefficient (log K_(PW) > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10~6 M~(-1) for PFOA and PFNA and 10~4 M~(-1) for perfluorodecanoate and perfluorooctane-sulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.