1242437-16-6Relevant academic research and scientific papers
Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains
Yang, Weizhun,Yoshida, Keisuke,Yang, Bo,Huang, Xuefei
, p. 180 - 194 (2016)
Proteoglycans play critical roles in many biological events. Due to their structural complexities, strategies towards synthesis of this class of glycopeptides bearing well-defined glycan chains are urgently needed. In this work, we give the full account o
Divergent Synthesis of Heparan Sulfate Oligosaccharides
Dulaney, Steven B.,Xu, Yongmei,Wang, Peng,Tiruchinapally, Gopinath,Wang, Zhen,Kathawa, Jolian,El-Dakdouki, Mohammad H.,Yang, Bo,Liu, Jian,Huang, Xuefei
, p. 12265 - 12279 (2016/01/09)
Heparan sulfates are implicated in a wide range of biological processes. A major challenge in deciphering their structure and activity relationship is the synthetic difficulties to access diverse heparan sulfate oligosaccharides with well-defined sulfation patterns. In order to expedite the synthesis, a divergent synthetic strategy was developed. By integrating chemical synthesis and two types of O-sulfo transferases, seven different hexasaccharides were obtained from a single hexasaccharide precursor. This approach combined the flexibility of chemical synthesis with the selectivity of enzyme-catalyzed sulfations, thus simplifying the overall synthetic operations. In an attempt to establish structure activity relationships of heparan sulfate binding with its receptor, the synthesized oligosaccharides were incorporated onto a glycan microarray, and their bindings with a growth factor FGF-2 were examined. The unique combination of chemical and enzymatic approaches expanded the capability of oligosaccharide synthesis. In addition, the well-defined heparan sulfate structures helped shine light on the fine substrate specificities of biosynthetic enzymes and confirm the potential sequence of enzymatic reactions in biosynthesis.
Chemical synthesis of a heparan sulfate glycopeptide: Syndecan-1
Yang, Bo,Yoshida, Keisuke,Yin, Zhaojun,Dai, Hang,Kavunja, Herbert,El-Dakdouki, Mohammad H.,Sungsuwan, Suttipun,Dulaney, Steven B.,Huang, Xuefei
supporting information, p. 10185 - 10189,5 (2012/12/12)
Finishing first: The highly complex structure of the title compound (see picture) was assembled. The protective groups utilized, as well as the sequences for formation of the glycosyl linkages and protecting group removal are critical to the success of the synthesis. This first preparation of a heparan sulfate glycopeptide lays the foundation for accessing other members of this class of molecules. Copyright
Divergent heparin oligosaccharide synthesis with preinstalled sulfate esters
Tiruchinapally, Gopinath,Yin, Zhaojun,El-Dakdouki, Mohammad,Wang, Zhen,Huang, Xuefei
experimental part, p. 10106 - 10112 (2011/10/18)
Traditional chemical synthesis of heparin oligosaccharides first involves assembly of the full length oligosaccharide backbone followed by sulfation. Herein, we report an alternative strategy in which the O-sulfate was introduced onto glycosyl building blocks as a trichloroethyl ester prior to assembly of the full length oligosaccharide. This allowed divergent preparation of both sulfated and non-sulfated building blocks from common advanced intermediates. The O-sulfate esters were found to be stable during glycosylation as well as typical synthetic manipulations encountered during heparin oligosaccharide synthesis. Furthermore, the presence of sulfate esters in both glycosyl donors and acceptors did not adversely affect the glycosylation yields, which enabled us to assemble multiple heparin oligosaccharides with preinstalled 6-O-sulfates. Copyright
Preactivation-based, one-pot combinatorial synthesis of heparin-like hexasaccharides for the analysis of heparin-protein interactions
Wang, Zhen,Xu, Yongmei,Yang, Bo,Tirachinapally, Gopinath,Sun, Bin,Liu, Renpeng,Dulaney, Steven,Liu, Jian,Huang, Xuefei
supporting information; experimental part, p. 8365 - 8375 (2010/09/07)
Heparin (HP) and heparan sulfate (HS) play important roles in many biological events. Increasing evidence has shown that the biological functions of HP and HS can be critically dependent upon their precise structures, including the position of the iduronic acids and sulfation patterns. However, unraveling the HP code has been extremely challenging due to the enormous structural variations. To overcome this hurdle, we investigated the possibility of assembling a library of HP/HS oligosaccharides using a preactivation-based, one-pot glycosylation method. A major challenge in HP/HS oligosaccharide synthesis is stereoselectivity in the formation of the cis-1,4-linkages between glucosamine and the uronic acid. Through screening, suitable protective groups were identified on the matching glycosyl donor and acceptor, leading to stereospecifie formation of both the cis-1,4- and trans-1,4-linkages present in HP. The protective group chemistry designed was also very flexible. From two advanced thioglycosyl disaccharide intermediates, all of the required disaccharide modules for library preparation could be generated in a divergent manner, which greatly simplified building-block preparation. Furthermore, the reactivity-independent nature of the preactivation-based, one-pot approach enabled us to mix the building blocks. This allowed rapid assembly of twelve HP/HS hexasaccharides with systematically varied and precisely controlled backbone structures in a combinatorial fashion. The speed and the high yields achieved in glycoassembly without the need to use a large excess of building blocks highlighted the advantages of our approach, which can be of general use to facilitate the study of HP/HS biology. As a proof of principle, this panel of hexasaccharides was used to probe the effect of backbone sequence on binding with the fibroblast growth factor-2 (FGF-2). A trisaccharide sequence of 2-O-sulfated iduronic acid flanked by N-sulfated glucosamines was identified to be the minimum binding motif and N-sulfation was found to be critical. This provides useful information for further development of more potent compounds towards FGF-2 binding, which can have potential applications in wound healing and anticancer therapy.
