Evaluating the affinity and kinetics of small molecule glycomimetics for human and mouse galectin-3 using surface plasmon resonance
(2023) In SLAS Discovery 28(5). p.233-239- Abstract
- Galectin-3 is a beta-galactoside-binding mammalian lectin that is one of a 15-member galectin family that can bind several cell surface glycoproteins via its carbohydrate recognition domain (CRD). As a result, it can influence a range of cellular processes including cell activation, adhesion and apoptosis. Galectin-3 has been implicated in various diseases, including fibrotic disorders and cancer, and is now being therapeutically targeted by both small and large molecules. Historically, the screening and triaging of small molecule glycomimetics that bind to the galectin-3 CRD has been completed in fluorescence polarisation (FP) assays to determine KD values. Surface plasmon resonance (SPR) has not been widely used for... (More)
- Galectin-3 is a beta-galactoside-binding mammalian lectin that is one of a 15-member galectin family that can bind several cell surface glycoproteins via its carbohydrate recognition domain (CRD). As a result, it can influence a range of cellular processes including cell activation, adhesion and apoptosis. Galectin-3 has been implicated in various diseases, including fibrotic disorders and cancer, and is now being therapeutically targeted by both small and large molecules. Historically, the screening and triaging of small molecule glycomimetics that bind to the galectin-3 CRD has been completed in fluorescence polarisation (FP) assays to determine KD values. Surface plasmon resonance (SPR) has not been widely used for compound screening and in this study it was used to compare human and mouse galectin-3 affinity measures between FP and SPR, as well as investigate compound kinetics. The KD estimates for a set of compounds selected from mono- and di-saccharides with affinities across a 550-fold range, correlated well between FP and SPR assay formats for both human and mouse galectin-3. Increases in affinity for compounds binding to human galectin-3 were driven by changes in both kon and koff whilst for mouse galectin-3 this was primarily due to kon. The reduction in affinity observed between human to mouse galectin-3 was also comparable between assay formats. SPR has been shown to be a viable alternative to FP for early drug discovery screening and determining KD values. In addition, it can also provide early kinetic characterisation of small molecule galectin-3 glycomimetics with robust kon and koff values generated in a high throughput manner. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8f9170dc-bf05-47c7-b093-3404c1d727ee
- author
- organization
- publishing date
- 2023-03-28
- type
- Contribution to journal
- publication status
- published
- subject
- in
- SLAS Discovery
- volume
- 28
- issue
- 5
- pages
- 233 - 239
- publisher
- SAGE Publications
- external identifiers
-
- pmid:36990319
- scopus:85151655901
- ISSN
- 2472-5552
- DOI
- 10.1016/j.slasd.2023.03.005
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2023 Galecto Biotech. Published by Elsevier Inc. All rights reserved.
- id
- 8f9170dc-bf05-47c7-b093-3404c1d727ee
- date added to LUP
- 2023-05-01 22:22:42
- date last changed
- 2024-07-14 06:32:06
@article{8f9170dc-bf05-47c7-b093-3404c1d727ee,
abstract = {{Galectin-3 is a beta-galactoside-binding mammalian lectin that is one of a 15-member galectin family that can bind several cell surface glycoproteins via its carbohydrate recognition domain (CRD). As a result, it can influence a range of cellular processes including cell activation, adhesion and apoptosis. Galectin-3 has been implicated in various diseases, including fibrotic disorders and cancer, and is now being therapeutically targeted by both small and large molecules. Historically, the screening and triaging of small molecule glycomimetics that bind to the galectin-3 CRD has been completed in fluorescence polarisation (FP) assays to determine <em>K<sub>D</sub></em> values. Surface plasmon resonance (SPR) has not been widely used for compound screening and in this study it was used to compare human and mouse galectin-3 affinity measures between FP and SPR, as well as investigate compound kinetics. The <em>K<sub>D</sub></em> estimates for a set of compounds selected from mono- and di-saccharides with affinities across a 550-fold range, correlated well between FP and SPR assay formats for both human and mouse galectin-3. Increases in affinity for compounds binding to human galectin-3 were driven by changes in both <em>k<sub>on</sub></em> and <em>k<sub>off</sub></em> whilst for mouse galectin-3 this was primarily due to <em>k<sub>on</sub></em>. The reduction in affinity observed between human to mouse galectin-3 was also comparable between assay formats. SPR has been shown to be a viable alternative to FP for early drug discovery screening and determining <em>K<sub>D</sub></em> values. In addition, it can also provide early kinetic characterisation of small molecule galectin-3 glycomimetics with robust <em>k<sub>on</sub></em> and <em>k<sub>off</sub></em> values generated in a high throughput manner.}},
author = {{Kim, Henry and Weidner, Nathalie and Ronin, Céline and Klein, Emmanuel and Roper, James A. and Kahl-Knutson, Barbro and Peterson, Kristoffer and Leffler, Hakon and Nilsson, Ulf J. and Pedersen, Anders and Zetterberg, Fredrik R. and Slack, Robert J.}},
issn = {{2472-5552}},
language = {{eng}},
month = {{03}},
number = {{5}},
pages = {{233--239}},
publisher = {{SAGE Publications}},
series = {{SLAS Discovery}},
title = {{Evaluating the affinity and kinetics of small molecule glycomimetics for human and mouse galectin-3 using surface plasmon resonance}},
url = {{http://dx.doi.org/10.1016/j.slasd.2023.03.005}},
doi = {{10.1016/j.slasd.2023.03.005}},
volume = {{28}},
year = {{2023}},
}