Glycodendrimers and Modified ELISAs: Tools to Elucidate Multivalent Interactions of Galectins 1 and 3

Wolfenden, Mark L.; Cousin, Jonathan G.; Nangia‐Makker, Pratima; Raz, Avraham; Cloninger, Mary J.

doi:10.3390/molecules20047059

Cited by 21 publications

(19 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mostly, Gal-3 binding was investigated for multivalent ligands based on chemical scaffolds like calixarenes, dendrimers or quantum dots [ 58 , 59 , 89 , 90 , 91 ]. Comparison of our results with findings for these synthetic scaffolds is difficult but can be drawn with regard to the glycan type and number.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3

2015

View full text Add to dashboard Cite

Carbohydrate-lectin interactions are relatively weak. As they play an important role in biological recognition processes, multivalent glycan ligands are designed to enhance binding affinity and inhibitory potency. We here report on novel neo-glycoproteins based on bovine serum albumin as scaffold for multivalent presentation of ligands for galectins. We prepared two kinds of tetrasaccharides (N-acetyllactosamine and N,N-diacetyllactosamine terminated) by multi-step chemo-enzymatic synthesis utilizing recombinant glycosyltransferases. Subsequent conjugation of these glycans to lysine groups of bovine serum albumin via squaric acid diethyl ester yielded a set of 22 different neo-glycoproteins with tuned ligand density. The neo-glycoproteins were analyzed by biochemical and chromatographic methods proving various modification degrees. The neo-glycoproteins were used for binding and inhibition studies with human galectin-3 showing high affinity. Binding strength and inhibition potency are closely related to modification density and show binding enhancement by multivalent ligand presentation. At galectin-3 concentrations comparable to serum levels of cancer patients, we detect the highest avidities. Selectivity of N,N-diacetyllactosamine terminated structures towards galectin-3 in comparison to galectin-1 is demonstrated. Moreover, we also see strong inhibitory potency of our scaffolds towards galectin-3 binding. These novel neo-glycoproteins may therefore serve as selective and strong galectin-3 ligands in cancer related biomedical research.

show abstract

Section: Resultsmentioning

confidence: 99%

“…It is assumed that Gal-3 assembles as pentamers (via the N-terminal domain) or oligomers (via the C-terminal domain) upon binding to its carbohydrate ligand [ 54 , 55 ]. Thus, multivalent presentation of ligands plays a role in effective binding of Gal-3 [ 56 , 57 , 58 , 59 ].…”

Section: Introductionmentioning

confidence: 99%

Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3

2015

View full text Add to dashboard Cite

show abstract

“…The binding strength of a lectin can be drastically increased by multivalent ligand presentation due to glyco clusters [ 66 , 67 , 68 , 69 , 70 ]. Gal-3 forms pentamers or oligomers during binding events [ 26 , 71 ], and multivalent carbohydrate presentation plays an important role in binding enhancement [ 66 , 72 , 73 , 74 ]. We recently demonstrated enhanced avidity of Gal-3 for multivalent presentation of LacdiNAc-terminated tetrasaccharides as neo-glycoproteins based on BSA [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

Biotinylated N-Acetyllactosamine- and N,N-Diacetyllactosamine-Based Oligosaccharides as Novel Ligands for Human Galectin-3

Böcker

Elling

2017

Bioengineering

View full text Add to dashboard Cite

Galectin inhibitor design is an emerging research field due to the involvement of galectins in cancer. Galectin-3, in particular, plays an important role in tumor progression. To generate inhibitors, modifications of the glycan structure can be introduced. Conjugation of hydrophobic compounds to saccharides has proven to be promising as increased binding of galectin-3 can be observed. In the present study, we report on neo-glycans carrying hydrophobic biotin as novel ligands for human galectin-3. We modified N-acetyllactosamine- and N,N-diacetyllactosamine-based tetrasaccharides at the C6-position of the terminal saccharide unit using selective enzymatic oxidation and subsequent chemical conjugation of biotinamidohexanoic acid hydrazide. These neo-glycans were much better bound by galectin-3 than the unmodified counterparts. High selectivity for galectin-3 over galectin-1 was also proven. We generated multivalent neo-glycoproteins by conjugation of neo-glycans to bovine serum albumin showing high affinity for galectin-3. Compared to non-biotinylated neo-glycoproteins, we achieved high binding levels of galectin-3 with a lesser amount of conjugated neo-glycans. Multivalent ligand presentation of neo-glycoproteins significantly increased the inhibitory potency towards galectin-3 binding to asialofetuin when compared to free monovalent glycans. Our findings show the positive impact of 6-biotinylation of tetrasaccharides on galectin-3 binding, which broadens the recent design approaches for producing high-affinity ligands.

show abstract

“…For example, the interaction of galectin-1 and surface adsorbed multivalent dendrimers 1 – 4 were investigated using an ELISA. The ELISA indicated that galectin-1 binds effectively to the glycodendrimers [ 152 ]. In addition, the binding of galectin-1 to glycodendrimers in solution was investigated using Dynamic Light Scattering (DLS) and Fluorescence Microscopy (FM) [ 89 ].…”

Section: Synthetic Multivalent Systems For Binding Of Galectin-1mentioning

confidence: 99%

The Role of Galectin-1 in Cancer Progression, and Synthetic Multivalent Systems for the Study of Galectin-1

Cousin

Cloninger

2016

IJMS

Self Cite

104

View full text Add to dashboard Cite

This review discusses the role of galectin-1 in the tumor microenvironment. First, the structure and function of galectin-1 are discussed. Galectin-1, a member of the galectin family of lectins, is a functionally dimeric galactoside-binding protein. Although galectin-1 has both intracellular and extracellular functions, the defining carbohydrate-binding role occurs extracellularly. In this review, the extracellular roles of galectin-1 in cancer processes are discussed. In particular, the importance of multivalent interactions in galectin-1 mediated cellular processes is reviewed. Multivalent interactions involving galectin-1 in cellular adhesion, mobility and invasion, tumor-induced angiogenesis, and apoptosis are presented. Although the mechanisms of action of galectin-1 in these processes are still not well understood, the overexpression of galectin-1 in cancer progression indicates that the role of galectin-1 is significant. To conclude this review, synthetic frameworks that have been used to modulate galectin-1 processes are reviewed. Small molecule oligomers of carbohydrates, carbohydrate-functionalized pseudopolyrotaxanes, cyclodextrins, calixarenes, and glycodendrimers are presented. These synthetic multivalent systems serve as important tools for studying galectin-1 mediated cancer cellular functions.

show abstract

Glycodendrimers and Modified ELISAs: Tools to Elucidate Multivalent Interactions of Galectins 1 and 3

Cited by 21 publications

References 91 publications

Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3

Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3

Biotinylated N-Acetyllactosamine- and N,N-Diacetyllactosamine-Based Oligosaccharides as Novel Ligands for Human Galectin-3

The Role of Galectin-1 in Cancer Progression, and Synthetic Multivalent Systems for the Study of Galectin-1

Contact Info

Product

Resources

About