A combined spectroscopic and crystallographic approach to probing drug-human serum albumin interactions.

David Buttar, Nicola Colclough, Stefan Gerhardt, Philip A MacFaul, Scott D Phillips, Alleyn Plowright, Paul Whittamore, Kin Tam, Klaus Maskos, Stefan Steinbacher, Holger Steuber

Index: Bioorg. Med. Chem. 18 , 7486-96, (2010)

Full Text: HTML

Abstract

The displacement of probes that bind selectively to subdomains IIA or IIIA on human serum albumin (HSA) by competing compounds has been followed using fluorescence spectroscopy, and has therefore been used to assign a primary binding site for these compounds in the presence and absence of fatty acids. The crystal structures have also been solved for three compounds: a matched pair of carboxylic acids whose binding strength to HSA unexpectedly decreased as the lipophilicity increased; and a highly bound sulphonamide that appeared not to displace the probes in the displacement assay. The crystallography results support the findings from the fluorescence displacement assay. The results indicate that drug binding to subdomain IB might also be important location for certain compounds.Copyright © 2010 Elsevier Ltd. All rights reserved.