Next Article in Journal
4D Flow Assessment of Vorticity in Right Ventricular Diastolic Dysfunction
Next Article in Special Issue
Use of Recombinant Mucin Glycoprotein to Assess the Interaction of the Gastric Pathogen Helicobacter pylori with the Secreted Human Mucin MUC5AC
Previous Article in Journal
So, You Think You Have an Idea: A Practical Risk Reduction-Conceptual Model for Academic Translational Research
Article Menu

Export Article

Open AccessArticle
Bioengineering 2017, 4(2), 31; doi:10.3390/bioengineering4020031

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

Laboratory for Biomaterials, Institute for Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstrasse 20, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
Received: 23 February 2017 / Revised: 28 March 2017 / Accepted: 31 March 2017 / Published: 5 April 2017
(This article belongs to the Special Issue Recombinant Glycoproteins)
View Full-Text   |   Download PDF [1321 KB, uploaded 5 April 2017]   |  

Abstract

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. View Full-Text
Keywords: biotin; chemo-enzymatic synthesis; galectin-3; LacdiNAc; neo-glycoprotein biotin; chemo-enzymatic synthesis; galectin-3; LacdiNAc; neo-glycoprotein
Figures

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. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Böcker, S.; Elling, L. Biotinylated N-Acetyllactosamine- and N,N-Diacetyllactosamine-Based Oligosaccharides as Novel Ligands for Human Galectin-3. Bioengineering 2017, 4, 31.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Bioengineering EISSN 2306-5354 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top