Synthesis of multivalent N-acetyl lactosamine modified quantum dots for the study of carbohydrate and galectin-3 interactions

Yang, Yang; Xue, Xiaochao; Jin, Xiaofeng; Wang, Lijun; Yan, Sha; Li, Zhongjun

doi:10.1016/j.tet.2012.06.035

Cited by 20 publications

(12 citation statements)

References 46 publications

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“…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%

“…Comparison of our results with findings for these synthetic scaffolds is difficult but can be drawn with regard to the glycan type and number. With multivalent LacNAc modified quantum-dots presenting 108 glycans, a 92-fold higher affinity towards Gal-3 in comparison to soluble LacNAc was shown using surface plasmon resonance spectroscopy [ 58 ]. With respect to one ligand, we gain higher enhancement of Gal-3 binding to BSA based neo-glycoproteins modified with a much smaller number of glycans, namely at least 14 LacDiNAc-LacNAc glycans ( 12f ).…”

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%

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

2015

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

2015

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“…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

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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.

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“…The results showed that the carbohydrate-coated QDs had good potential for in vivo targeting. Yang et al (2012) have prepared N-acetyl lactosamine, bivalent N-acetyl lactosamine, and N-acetyl lactosamine coated QDs as a fluorescent probe to study the interactions of N-acetyl lactosamine and galectin-3 ( Figure 1).…”

Section: Glyco-quantum Dotsmentioning

confidence: 99%

The glyconanoparticle as carrier for drug delivery

Zhang

Huang

2018

Drug Delivery

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The glyconanoparticle (GlycoNP) has multiple effects and has important applications in drug delivery and bioimaging. It not only has the advantages of nano drug delivery system but also utilizes the characteristics of multivalent interaction of sugar, which greatly improves the targeting of drug delivery. Herein, the application of GlycoNP in drug delivery was analyzed and discussed, the solution to its problem was proposed, and its prospects were forecasted. ARTICLE HISTORY

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Synthesis of multivalent N-acetyl lactosamine modified quantum dots for the study of carbohydrate and galectin-3 interactions

Cited by 20 publications

References 46 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 glyconanoparticle as carrier for drug delivery

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