Combined magnetic ligand fishing and high-resolution inhibition profiling for identification of α-glucosidase inhibitory ligands: A new screening approach based on complementary inhibition and affinity profiles.

Sileshi Gizachew Wubshet; Bingrui Liu; Kenneth Thermann Kongstad; Ulrike Böcker; Malene Johanne Petersen; Tuo Li; Junru Wang; Dan Stærk

doi:10.1016/j.talanta.2019.03.047

Combined magnetic ligand fishing and high-resolution inhibition profiling for identification of α-glucosidase inhibitory ligands: A new screening approach based on complementary inhibition and affinity profiles.

Sileshi Gizachew Wubshet, Bingrui Liu, Kenneth Thermann Kongstad, Ulrike Böcker, Malene Johanne Petersen, Tuo Li, Junru Wang, Dan Stærk

8 Citations (Scopus)

Abstract

Plants are well-recognized sources of inhibitors for α-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 α-glucosidase inhibitors from complex plant extracts. Non-specific affinities and non-specific inhibitions are major sources of false positive hits from ligand fishing and high-resolution 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 identify α-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, α-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.

Original language	English
Journal	Talanta
Volume	200
Pages (from-to)	279-287
ISSN	0039-9140
DOIs	https://doi.org/10.1016/j.talanta.2019.03.047
Publication status	Published - 1 Aug 2019

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Wubshet, S. G., Liu, B., Kongstad, K. T., Böcker, U., Petersen, M. J., Li, T., Wang, J., & Stærk, D. (2019). Combined magnetic ligand fishing and high-resolution inhibition profiling for identification of α-glucosidase inhibitory ligands: A new screening approach based on complementary inhibition and affinity profiles. Talanta, 200, 279-287. https://doi.org/10.1016/j.talanta.2019.03.047

Combined magnetic ligand fishing and high-resolution inhibition profiling for identification of α-glucosidase inhibitory ligands: A new screening approach based on complementary inhibition and affinity profiles. / Wubshet, Sileshi Gizachew; Liu, Bingrui; Kongstad, Kenneth Thermann et al.

In: Talanta, Vol. 200, 01.08.2019, p. 279-287.

Research output: Contribution to journal › Journal article › Research › peer-review

Wubshet, SG, Liu, B, Kongstad, KT, Böcker, U, Petersen, MJ, Li, T, Wang, J & Stærk, D 2019, 'Combined magnetic ligand fishing and high-resolution inhibition profiling for identification of α-glucosidase inhibitory ligands: A new screening approach based on complementary inhibition and affinity profiles.', Talanta, vol. 200, pp. 279-287. https://doi.org/10.1016/j.talanta.2019.03.047

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title = "Combined magnetic ligand fishing and high-resolution inhibition profiling for identification of α-glucosidase inhibitory ligands: A new screening approach based on complementary inhibition and affinity profiles.",

abstract = "Plants are well-recognized sources of inhibitors for α-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 α-glucosidase inhibitors from complex plant extracts. Non-specific affinities and non-specific inhibitions are major sources of false positive hits from ligand fishing and high-resolution 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 identify α-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, α-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. ",

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AU - Wubshet, Sileshi Gizachew

AU - Liu, Bingrui

AU - Kongstad, Kenneth Thermann

AU - Böcker, Ulrike

AU - Petersen, Malene Johanne

AU - Li, Tuo

AU - Wang, Junru

AU - Stærk, Dan

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N2 - Plants are well-recognized sources of inhibitors for α-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 α-glucosidase inhibitors from complex plant extracts. Non-specific affinities and non-specific inhibitions are major sources of false positive hits from ligand fishing and high-resolution 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 identify α-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, α-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.

AB - Plants are well-recognized sources of inhibitors for α-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 α-glucosidase inhibitors from complex plant extracts. Non-specific affinities and non-specific inhibitions are major sources of false positive hits from ligand fishing and high-resolution 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 identify α-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, α-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.

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