albumin - publications

Predict more albumin - ligand interactions now!


1. Drug Metab Dispos. 2012 Apr 18. [Epub ahead of print]

Interaction Between Two Sulfate Conjugated Uremic Toxins, p-cresyl Sulfate and
Indoxyl Sulfate, During Binding with Human Serum Albumin.

Watanabe H, Noguchi T, Miyamoto Y, Kadowaki D, Kotani S, Nakajima M, Miyamura S,
Ishima Y, Otagiri M, Maruyama T.

1 Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences,
Kumamoto University;

Recently, p-cresyl sulfate (PCS) has been identified as a protein bound uremic
toxin. Moreover, the serum free concentration of PCS, which is associated with
its efficacy of hemodialysis, appears to be a good predictor of survival in
chronic kidney disease (CKD). We previously found that PCS interacts with indoxyl
sulfate (IS), another sulfate conjugated uremic toxin, during renal excretion via
a common transporter. The purpose of this study was to further investigate the
interaction between PCS and IS on the binding to human serum albumin (HSA). Here,
we used ultrafiltration to show that there is only one high affinity binding site
for PCS, with a binding constant in the order of 10(5) M(-1 )(i.e. comparable to
IS). However, a binding constant of low affinity binding site for PCS is 2.5-fold
greater than that for IS. Displacement of a fluorescence probe showed that PCS
mainly binds to site II, which is the high affinity site for PCS, on HSA. This
finding was further supported by experiments using mutant HSA (R410A/Y411A) that
displayed reduced site II ligand binding. A Klotz analysis showed that there
could be a competitive inhibition between PCS and IS on HSA binding. Similar
interaction between PCS and IS on HSA was also observed under the conditions
mimic CKD stage 4-5. The present study suggests that competitive interactions
between PCS and IS in both HSA binding and the renal excretion process could
contribute to fluctuations in their free serum concentrations in CKD patients.

PMID: 22513409 [PubMed - as supplied by publisher]