es6b00484_si_001.pdf (3.03 MB)
Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin
journal contribution
posted on 2016-04-26, 00:00 authored by Eric A. Rodriguez, Xueshu Li, Hans-Joachim Lehmler, Larry
W. Robertson, Michael W. DuffelThe 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.