Highly stabilized, polymer-lipid membranes prepared on silica microparticles as stationary phases for capillary chromatography.

Autor: Gallagher ES; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States., Adem SM; Department of Chemistry, Washburn University, Topeka, KS 66621, United States., Baker CA; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States., Ratnayaka SN; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States., Jones IW; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States., Hall HK Jr; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States., Saavedra SS; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Bio5 Institute, University of Arizona, Tucson, AZ 85721, United States., Aspinwall CA; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, United States; Bio5 Institute, University of Arizona, Tucson, AZ 85721, United States; Department of Biomedical Engineering, University of Arizona, Tucson, AZ 85721, United States. Electronic address: aspinwal@email.arizona.edu.
Jazyk: angličtina
Zdroj: Journal of chromatography. A [J Chromatogr A] 2015 Mar 13; Vol. 1385, pp. 28-34. Date of Electronic Publication: 2015 Jan 24.
DOI: 10.1016/j.chroma.2015.01.052
Abstrakt: The ability to rapidly screen complex libraries of pharmacological modulators is paramount to modern drug discovery efforts. This task is particularly challenging for agents that interact with lipid bilayers or membrane proteins due to the limited chemical, physical, and temporal stability of conventional lipid-based chromatographic stationary phases. Here, we describe the preparation and characterization of a novel stationary phase material composed of highly stable, polymeric-phospholipid bilayers self-assembled onto silica microparticles. Polymer-lipid membranes were prepared by photochemical or redox initiated polymerization of 1,2-bis[10-(2',4'-hexadieoyloxy)decanoyl]-sn-glycero-2-phosphocholine (bis-SorbPC), a synthetic, polymerizable lipid. The resulting polymerized bis-SorbPC (poly(bis-SorbPC)) stationary phases exhibited enhanced stability compared to particles coated with 1,2-dioleoyl-sn-glycero-phosphocholine (unpolymerized) phospholipid bilayers when exposed to chemical (50 mM triton X-100 or 50% acetonitrile) and physical (15 min sonication) insults after 30 days of storage. Further, poly(bis-SorbPC)-coated particles survived slurry packing into fused silica capillaries, compared to unpolymerized lipid membranes, where the lipid bilayer was destroyed during packing. Frontal chromatographic analyses of the lipophilic small molecules acetylsalicylic acid, benzoic acid, and salicylic acid showed >44% increase in retention times (P<0.0001) for all analytes on poly(bis-SorbPC)-functionalized stationary phase compared to bare silica microspheres, suggesting a lipophilic retention mechanism. Phospholipid membrane-functionalized stationary phases that withstand the chemical and physical rigors of capillary LC conditions can substantially increase the efficacy of lipid membrane affinity chromatography, and represents a key advance toward the development of robust membrane protein-functionalized chromatographic stationary phases.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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