Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin.
The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl-l-proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≥ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity.
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa , Iowa City, Iowa 52246, United States.
Eric A
EA
Rodriguez
Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52246, United States.
Xueshu
X
Li
Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52246, United States.
Hans-Joachim
HJ
Lehmler
Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52246, United States.
Larry W
LW
Robertson
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa , Iowa City, Iowa 52246, United States.
Michael W
MW
Duffel
D001665:Binding Sites; D003619:Dansyl Compounds; D054879:Halogenation; D006801:Humans; D006900:Hydroxylation; D055585:Physical Phenomena; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D011228:Prealbumin / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives; D012709:Serum Albumin / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism
D003619:Dansyl Compounds; D011228:Prealbumin; D012709:Serum Albumin; D013431:Sulfates; C086697:dansylproline; D011392:Proline; D011078:Polychlorinated Biphenyls; D013974:Thyroxine