Synthetic Human Serum Albumin Sudlow I Binding Site Mimics
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
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.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-139395DOI: 10.1021/jm100491vISI: 000284287200004PubMedID: 20973485OAI: oai:DiVA.org:uu-139395DiVA: diva2:381303