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Synthetic Human Serum Albumin Sudlow I Binding Site Mimics
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. (BBCL ; PPL ; BMC)ORCID iD: 0000-0002-7392-0591
Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. (BBCL)
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2010 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 53, no 22, 7932-7937 p.Article in journal (Refereed) Published
Abstract [en]

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 (H-1 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.

Place, publisher, year, edition, pages
2010. Vol. 53, no 22, 7932-7937 p.
Keyword [en]
warfarin, molecularly imprinted polymer, biomaterial, HSA, molecular recognition
National Category
Other Basic Medicine
Research subject
Chemistry, Organic Chemistry
Identifiers
URN: urn:nbn:se:lnu:diva-8991DOI: 10.1021/jm100491vOAI: oai:DiVA.org:lnu-8991DiVA: diva2:357349
Projects
VRKKSCrafoord Foundation
Available from: 2010-10-18 Created: 2010-10-18 Last updated: 2017-02-10Bibliographically approved

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Karlsson, Björn C. G.Rosengren, Annika M.Nicholls, Ian A.
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CiteExportLink to record
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Citation style
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