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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Galectin 1*/metabolism ; Galectin 1*/antagonists & inhibitors ; Galectin 1*/chemistry ; Surface Plasmon Resonance*/methods ; Protein Binding*; Humans ; Animals ; Mice ; Kinetics ; Small Molecule Libraries/pharmacology ; Small Molecule Libraries/chemistry ; Fluorescence Polarization/methods

The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), to 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 used fluorescence polarization (FP) assays to determine K D 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 1000-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 in 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.

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N/A Galecto (Denmark)

Keywords: fluorescence polarization; galectin-1; small molecule glycomimetics; surface plasmon resonance

0 (Galectin 1)
0 (Small Molecule Libraries)
0 (LGALS1 protein, human)

Date Created: 20240627 Date Completed: 20240627 Latest Revision: 20240717

20240717

PMC11203799

10.3390/ijms25126704

38928409