Synthetic Human Serum Albumin Sudlow I Binding Site Mimics
journal contributionposted on 2010-11-25, 00:00 authored by Björn C. G. Karlsson, Annika M. Rosengren, Inga Näslund, Per Ola Andersson, Ian A. Nicholls
Here, we report the design, synthesis, and characterization of molecularly imprinted polymer (MIP) derived mimics of the human serum albumin (HSA) Sudlow I sitethe binding site for the anticoagulant warfarin. MIP design was based upon a combination of experimental (1H NMR) and computational (molecular dynamics) methods. Two MIPs and corresponding nonimprinted reference polymers were synthesized and characterized (scanning electron microscopy; nitrogen sorption; and Fourier transform infrared spectroscopy). MIP−ligand recognition was examined using radioligand binding studies, where the largest number of selective sites was found in a warfarin-imprinted methacrylic acid−ethylene dimethacrylate copolymer (MAA-MIP). The warfarin selectivity of this MIP was confirmed using radioligand displacement and zonal chromatographic studies. A direct comparison of MIP−warfarin binding characteristics with those of the HSA Sudlow I binding site was made, and similarities in site population (per gram polymer or protein) and affinities were observed. The warfarin selectivity of the MIP suggests its potential for use as a recognition element in a MIP-based warfarin sensor and even as a model to aid in understanding and steering blood−plasma protein-regulated transport processes or even for the development of warfarin sensors.