Synthetic human serum albumin Sudlow I binding site mimics.
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 ((1)H 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.
Karlsson
Björn C G
BC
Bioorganic and Biophysical Chemistry Laboratory, School of Natural Sciences, Linnæus University, SE-391 82 Kalmar, Sweden.
Rosengren
Annika M
AM
Näslund
Inga
I
Andersson
Per Ola
PO
Nicholls
Ian A
IA
D000925:Anticoagulants / Q000737:chemistry; D001665:Binding Sites; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D054802:Molecular Imprinting; D018716:Molecular Mimicry; D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D011869:Radioligand Assay; D012709:Serum Albumin / Q000737:chemistry*; D014859:Warfarin / Q000737:chemistry
D000925:Anticoagulants; D008024:Ligands; D011109:Polymethacrylic Acids; D012709:Serum Albumin; D014859:Warfarin