Grant, Oliver C. and Smith, Hannah M.K. and Firsova, Daria and Fadda, Elisa and Woods, Robert J.
(2014)
Presentation, presentation, presentation! Molecular-level
insight into linker effects on glycan array screening data.
Glycobiology, 24 (1).
pp. 17-25.
ISSN 0959-6658
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.
Item Type: |
Article
|
Additional Information: |
This is the postprint version of the published article. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/
3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use,
please contact journals.permissions@oup.com |
Keywords: |
glycan array screening; glycan-binding
protein; glycan specificity; linker effects; molecular dynamics; |
Academic Unit: |
Faculty of Science and Engineering > Chemistry |
Item ID: |
6990 |
Identification Number: |
https://doi.org/10.1093/glycob/cwt083 |
Depositing User: |
Elisa Fadda
|
Date Deposited: |
26 Feb 2016 15:02 |
Journal or Publication Title: |
Glycobiology |
Publisher: |
Oxford University Press |
Refereed: |
Yes |
URI: |
|
Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
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