Combined magnetic ligand fishing and high-resolution inhibition profiling for identification of α-glucosidase inhibitory ligands: A new screening approach based on complimentary inhibition and affinity profiles
Wubshet, Sileshi Gizachhew; Liu, Bingrui; Kongstad, Kenneth T.; Böcker, Ulrike; Petersen, Malene J.; Li, Tuo; Wang, Junru; Staerk, Dan
Journal article, Peer reviewed
Accepted version
Permanent lenke
http://hdl.handle.net/11250/2593069Utgivelsesdato
2019Metadata
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Originalversjon
Talanta: The International Journal of Pure and Applied Analytical Chemistry. 2019, 200 279-287. 10.1016/j.talanta.2019.03.047Sammendrag
Plants are well-recognized sources of inhibitors for -glucosidase - a key target enzyme for management of type 2 diabetes. Recently, two advanced bioactivity-profiling techniques, i.e., ligand fishing and high-resolution inhibition profiling, have shown great promises for accelerating identification of -glucosidase inhibitors from complex plant extracts. Non-specific affinities and non-specific inhibitions are major sources of false positive hits from ligand fishing and highresolution inhibition profiling, respectively. In an attempt to minimize such false positive hits, we describe a new screening approach based on ligand fishing and high-resolution inhibition profiling for detection of high-affinity ligands and assessment of inhibitory activity, respectively. The complementary nature of ligand fishing and high-resolution inhibition profiling was explored to Manuscript for Talanta 3 identify-glucosidase inhibitory ligands from a complex mixture, and proof-of-concept was demonstrated with crude ethyl acetate extract of Ginkgo biloba. In addition to magnetic beads with a 3-carbon aliphatic linker, -glucosidase was immobilized on magnetic beads with a 21-carbon aliphatic linker; and the two different types of magnetic beads were compared for their hydrolytic activity and fishing efficiency.