Generation of α-Linked Oligosaccharide Libraries by Random
Glycosylation on Unprotected Acceptors
Yili Ding
1*
, Chamakura VNS Varaprasad
2
, Saeed El-Ashram
1
, Jiedan Liao
1
, Nan Zhang
1
, Shujian Huang
1
and Bingyun Wang
1
1
Life Science Department, Foshan University, Foshan, Guangdong, China
2
Das Pharma, Turangi, Kakinada, Andhra Pradesh, India
*Corresponding author: Ding Y, Life Science Department, Foshan University, Foshan, Guangdong, China, Tel: +13052299170; E-mail: yiding93@yahoo.com
Received date: February 07, 2018; Accepted date: February 21, 2018; Published date: February 25, 2018
Copyright: © 2018 Ding Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background
Te GlcNAc related disaccharides were reported to show inhibitory activity on breast tumor cells (MDA-
MB-231). However, synthesis of disaccharides is lengthy, laborious and time consuming, and it is necessary to fnd
more efcient methods to generate the disaccharide libraries. Random glycosylation has been an established
practice to generate β-linked disaccharides library. Synthesis of α-linked disaccharide libraries by random
glycosylation hasn’t been explored yet. We present our results on the synthesis of α-linked GlcNAc related
disaccharide libraries by random glycosylation in this article.
Results
Employing random glycosylation as a key step on an unprotected GlcNAc monosaccharide, and afer
deprotection and careful purifcation, few α-linked GlcNAc related disaccharide libraries were obtained in
acceptable ratios, and the results were confrmed by mass and NMR spectral data.
Conclusion
Random glycosylation was demonstrated as an efcient method for the synthesis of α-linked GlcNAc related
oligosaccharide libraries.
Keywords: Oligosaccharide; Random glycosylation; Combinatorial
chemistry; α-Linked GlcNAc oligosaccharide library
Introduction
Interaction between cell surface carbohydrate ligands and various
protein receptors forms the basis of recognition events, which are
fundamental to vastly diverse range of biological and pathological
processes [1]. Cell surface carbohydrates constitute efcient receptors
for hormones, toxins, bacteria and viruses [2]. Terefore, synthetic
oligosaccharides can be screened as cell adhesion inhibitors or antigens
from which specifc antibodies can be triggered. However,
oligosaccharides are very complex and diverse, and their synthesis is
both lengthy and expensive [3]. Recent research showed that the most
important residue in the structures of oligosaccharide epitopes
recognized by the antibodies are the terminal fragments which
normally are disaccharides, trisaccharides or tetrasaccharides [4]. Tis
fact elicited lot of interest to synthesize a diverse array of small size (di,
tri and tetra) oligosaccharide libraries for studying their biological
properties instead of synthesizing the whole size oligosaccharides.
Specifc disaccharides have been identifed as markers for certain
types of tumors. For example, the chondroitin sulfate disaccharides
were reported to show inhibitory activity on breast tumor cells (MDA-
MB-231) [5], 16 chondroitin sulfate disaccharides were tested on the
more aggressive MDA-MB-231 cell line, a statistically signifcant
decrease in cell viability was observed for some of disaccharides at 100
μg/mL concentration, and the results indicated that both the number
and position of the sulfate groups present in the chondroitin sulfate
disaccharide have an efect on MDA-MB-231 cell viability. Tese
results stimulated lot of interest among chemists to fnd the more
efcient methods to synthesize the small sulfated oligosaccharide
libraries.
Accordingly, using an orthogonal protection strategy, sulfated Gal-
β1,3/4-GlcNAc disaccharide library was reported by Tu et al. [6], while
synthesis of 48 disaccharide building blocks for assembling of a
heparin oligosaccharide library was achieved by Hung research group
[7]. Further, from a common intermediate possessing orthogonally
removable protective groups, all 16 disaccharide sulfates were
systematically synthesized by Suda et al. [8]. Tese syntheses are both
lengthy and time consuming, and there is a large scope to fnd more
efcient methods for generating the oligosaccharide libraries.
Random glycosylation on unprotected glycosylation acceptors can
generate oligosaccharide libraries containing all possible
oligosaccharides with certain confguration [9]. Random
galactosylation on an unprotected GlcNAc acceptor generated all six-
possible disaccharide library with α and β linkages, and six
disaccharides were chemically synthesized to compare with the library
in HPLC to confrm the results [10]. Te ratio of six disaccharides is
not good enough for their biological activity evaluation, even many
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ISSN: 2161-0401
Organic Chemistry: Current Research
Ding et al., Organic Chem Curr Res 2018, 7:1
DOI: 10.4172/2161-0401.1000188
Research Article Open Access
Organic Chem Curr Res, an open access journal
ISSN: 2161-0401
Volume 7 • Issue 1 • 1000188