Presentation, presentation, presentation! Molecular-level insight into linker effects on glycan array screening data
Presentation, presentation, presentation! Molecular-level insight into linker effects on glycan array screening data
Changes in cell-surface glycan patterns are markers of the presence of many different disease and cancer types, offering a relatively untapped niche for glycan-targeting reagents and therapeutics in diagnosis and treatment. Of paramount importance for the success of any glycan-targeting reagent is the ability to specifically recognize the target among the plethora of different glycans that exist in the human body. The preeminent technique for defining specificity is glycan array screening, in which a glycan-binding protein (GBP) can be simultaneously screened against multiple glycans. Glycan array screening has provided unparalleled insight into GBP specificity, but data interpretation suffers from difficulties in identifying false-negative binding arising from altered glycan presentation, associated with the linker used to conjugate the glycan to the surface. In this work, we model the structure and dynamics of the linkers employed in the glycan arrays developed by the Consortium for Functional Glycomics. The modeling takes into account the physical presence and surface polarity of the array, and provides a structure-based rationalization of false-negative results arising from the so-called "linker effect." The results also serve as a guide for interpreting glycan array screening data in a biological context; in particular, we show that attempts to employ natural amino acids as linkers may be prone to unexpected artifacts compromising glycan recognition.
glycan array screening, glycan specificity, glycan-binding protein, linker effects, molecular dynamics
17-25
Grant, Oliver C.
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Smith, Hannah M.K.
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Firsova, Daria
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Fadda, Elisa
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Woods, Robert J.
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1 January 2014
Grant, Oliver C.
fa8de877-5a52-4160-8352-3e0ac6f74d57
Smith, Hannah M.K.
e97b320e-8bee-4b80-84e5-d7da65e1e723
Firsova, Daria
7cf99310-e4f3-4913-8210-e3062874bfbc
Fadda, Elisa
11ba1755-9585-44aa-a38e-a8bcfd766abb
Woods, Robert J.
e3e3113b-203f-41ee-8aeb-92db4882c3ca
Grant, Oliver C., Smith, Hannah M.K., Firsova, Daria, Fadda, Elisa and Woods, Robert J.
(2014)
Presentation, presentation, presentation! Molecular-level insight into linker effects on glycan array screening data.
Glycobiology, 24 (1), .
(doi:10.1093/glycob/cwt083).
Abstract
Changes in cell-surface glycan patterns are markers of the presence of many different disease and cancer types, offering a relatively untapped niche for glycan-targeting reagents and therapeutics in diagnosis and treatment. Of paramount importance for the success of any glycan-targeting reagent is the ability to specifically recognize the target among the plethora of different glycans that exist in the human body. The preeminent technique for defining specificity is glycan array screening, in which a glycan-binding protein (GBP) can be simultaneously screened against multiple glycans. Glycan array screening has provided unparalleled insight into GBP specificity, but data interpretation suffers from difficulties in identifying false-negative binding arising from altered glycan presentation, associated with the linker used to conjugate the glycan to the surface. In this work, we model the structure and dynamics of the linkers employed in the glycan arrays developed by the Consortium for Functional Glycomics. The modeling takes into account the physical presence and surface polarity of the array, and provides a structure-based rationalization of false-negative results arising from the so-called "linker effect." The results also serve as a guide for interpreting glycan array screening data in a biological context; in particular, we show that attempts to employ natural amino acids as linkers may be prone to unexpected artifacts compromising glycan recognition.
Text
cwt083
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Accepted/In Press date: 15 September 2013
e-pub ahead of print date: 20 September 2013
Published date: 1 January 2014
Keywords:
glycan array screening, glycan specificity, glycan-binding protein, linker effects, molecular dynamics
Identifiers
Local EPrints ID: 499799
URI: http://eprints.soton.ac.uk/id/eprint/499799
ISSN: 0959-6658
PURE UUID: 47139305-5dc0-4ec5-b2e2-307017838f91
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Date deposited: 04 Apr 2025 16:40
Last modified: 22 Aug 2025 02:42
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Contributors
Author:
Oliver C. Grant
Author:
Hannah M.K. Smith
Author:
Daria Firsova
Author:
Elisa Fadda
Author:
Robert J. Woods
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