Preprint Communication Version 1 Preserved in Portico This version is not peer-reviewed

Determining the Affinity and Kinetics of Small Molecule Inhibitors of Galectin-1 Using Surface Plasmon Resonance

Henry Kim
,
Louis Kretz
,
Celine Ronin
,
Christina Starck
,
James A. Roper
,
Barbro Kahl-Knutson
,
Kristoffer Peterson
ORCID logo ,
Hakon Leffler
ORCID logo ,
Ulf J. Nilsson
ORCID logo ,
Anders Pedersen
,
Fredrik R. Zetterberg
,
Robert J. Slack
* ORCID logo
Version 1 : Received: 15 April 2024 / Approved: 16 April 2024 / Online: 16 April 2024 (10:01:02 CEST)

How to cite: Kim, H.; Kretz, L.; Ronin, C.; Starck, C.; Roper, J.A.; Kahl-Knutson, B.; Peterson, K.; Leffler, H.; Nilsson, U.J.; Pedersen, A.; Zetterberg, F.R.; Slack, R.J. Determining the Affinity and Kinetics of Small Molecule Inhibitors of Galectin-1 Using Surface Plasmon Resonance. Preprints 2024, 2024041027. https://doi.org/10.20944/preprints202404.1027.v1 Kim, H.; Kretz, L.; Ronin, C.; Starck, C.; Roper, J.A.; Kahl-Knutson, B.; Peterson, K.; Leffler, H.; Nilsson, U.J.; Pedersen, A.; Zetterberg, F.R.; Slack, R.J. Determining the Affinity and Kinetics of Small Molecule Inhibitors of Galectin-1 Using Surface Plasmon Resonance. Preprints 2024, 2024041027. https://doi.org/10.20944/preprints202404.1027.v1

Abstract

The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), various cell surface glycoproteins and has been implicated in a range of cancers. As a consequence of binding to sugar residues on cell surface receptors it has been shown to have a pleiotropic effect across many cell types and mechanisms resulting in immune system modulation and cancer progression. As a result, it has started to become a therapeutic target for both small and large molecules. In previous studies, we have used fluorescence polarisation (FP) assays to determine KD values to screen and triage small molecule glycomimetics that bind to the galectin-1 CRD. In this study surface plasmon resonance (SPR) was used to compare human and mouse galectin-1 affinity measures with FP as SPR has not been applied for compound screening against this galectin. Binding affinities for a selection of mono- and di-saccharides covering a 1,000-fold range correlated well between FP and SPR assay formats for both human and mouse galectin-1. It was shown that slower dissociation drove the increased affinity at human galectin-1 whilst faster association was responsible for the effects at mouse galectin-1. This study demonstrates that SPR is a sound alternative to FP for early drug discovery screening and determining affinity estimates. Consequently, it also allows association and dissociation constants to be measured in a high throughput manner for small molecule galectin-1 inhibitors.

Keywords

galectin-1; small molecule glycomimetics; surface plasmon resonance; fluorescence polarisation

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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