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Reference type: Journal
Authors: Karlsson BCG, Rosengren AM, Näslund I, Andersson PO, Nicholls IA
Article Title: Synthetic Human Serum Albumin Sudlow I Binding Site Mimics.
Publication date: 2010
Journal: Journal of Medicinal Chemistry
Volume: 53
Issue: (22)
Page numbers: 7932-7937.
DOI: 10.1021/jm100491v

Abstract: Here, we report the design, synthesis, and characterization of molecularly imprinted polymer (MIP) derived mimics of the human serum albumin (HSA) Sudlow I site - the 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
Template and target information: warfarin


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