Chemoenzymatic design of heparan sulfate oligosaccharides.
Heparan sulfate is a sulfated glycan that exhibits essential physiological functions. Interrogation of the specificity of heparan sulfate-mediated activities demands a library of structurally defined oligosaccharides. Chemical synthesis of large heparan sulfate oligosaccharides remains challenging. We report the synthesis of oligosaccharides with different sulfation patterns and sizes from a disaccharide building block using glycosyltransferases, heparan sulfate C(5)-epimerase, and sulfotransferases. This method offers a generic approach to prepare heparan sulfate oligosaccharides possessing predictable structures.
Liu
Renpeng
R
Division of Medicinal Chemistry and Natural Products, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Xu
Yongmei
Y
Chen
Miao
M
Weïwer
Michel
M
Zhou
Xianxuan
X
Bridges
Arlene S
AS
DeAngelis
Paul L
PL
Zhang
Qisheng
Q
Linhardt
Robert J
RJ
Liu
Jian
J
D000991:Antithrombins / Q000737:chemistry; D002238:Carbohydrate Epimerases / Q000737:chemistry; D002240:Carbohydrate Sequence; D002621:Chemistry / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004187:Disaccharides / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary
D000991:Antithrombins; D002238:Carbohydrate Epimerases; D004187:Disaccharides; D006497:Heparan Sulfate; D009844:Oligosaccharides; D011134:Polysaccharides; C430881:heparin-heparan sulfate-glucuronic acid C5-epimerase