Strategies in Synthesis of Heparin/Heparan Sulfate Oligosaccharides

Dulaney, Steven B.; Huang, Xuefei

doi:10.1016/b978-0-12-396527-1.00003-6

Cited by 82 publications

(46 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…63–65 However, this disaccharide moiety does contain the synthetically challenging α (1,4) glycosidic linkage. 66 …”

Section: Resultsmentioning

confidence: 99%

“…The method overcomes the limitations previously associated with the stereoselective coupling of the electron-poor glucuronic acid acceptor with a glucosamine-derived donor. 66 Next, selective hydrolysis of the C(6)-acetyl group in disaccharide 11 was examined. Fortunately, subjection of 11 to NaOMe for 2 h at 25 °C produced the disaccharide-containing primary alcohol intermediate, whose N -benzylidene protecting group was then removed with HCl in acetone.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers

Sletten

Loka

et al. 2017

Biomacromolecules

View full text Add to dashboard Cite

We report herein the first-time exploration of the attachment of well-defined saccharide units onto a synthetic polymer backbone for the inhibition of a glycosidase. More specifically, glycopolymers endowed with heparan sulfate (HS) disaccharides were established to inhibit the glycosidase, heparanase, with an IC50 value in the low nanomolar range (1.05 ± 0.02 nm), a thousand-fold amplification over its monovalent counterpart. The monomeric moieties of these glycopolymers were designed in silico to manipulate the well-established glycotope of heparanase into an inhitope. Studies concluded that (1) the glycopolymers are hydrolytic stable toward heparanase, (2) longer polymer length provides greater inhibition, and (3) increased local saccharide density (monoantennary vs diantennary) is negligible due to hindered active site of heparanase. Furthermore, HS oligosaccharide and polysaccharide controls illustrate the enhanced potency of a multivalent scaffold. Overall, the results on these studies of the multivalent presentation of saccharides on bottlebrush polymers serve as the platform for the design of potent glycosidase inhibitors and have potential to be applied to other HS-degrading proteins.

show abstract

“…63–65 However, this disaccharide moiety does contain the synthetically challenging α (1,4) glycosidic linkage. 66 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers

Sletten

Loka

et al. 2017

Biomacromolecules

View full text Add to dashboard Cite

show abstract

“…Due to the 1,2- cis -2-amino linkage nature of the GlcNS(6S)α(1,4)GlcA disaccharide unit, control of its stereoselective formation is quite challenging. 21 Capitalizing on our reported nickel-catalyzed 1,2- cis -2-aminoglycoside methodology, 22 we investigated the direct coupling of GlcA acceptor 7 with GlcN donors 4 – 6 (Scheme 1) having pivaloyl (Piv), triethylsilyl (TES), and benzyl (Bn) groups, respectively, at O -4. Under our nickel conditions, disaccharides 9–11 were formed in 52–85% yield with exclusive α-selectivity.…”

mentioning

confidence: 99%

Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity

Loka

Sletten

et al. 2017

Chem. Commun.

View full text Add to dashboard Cite

Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics. This glycopolymer also lacks anticoagulant activity.

show abstract

“…7–9 In comparison, methodologies for the preparation of glycopeptides carrying homogenous glycosaminoglycan are under developed. Much synthetic work related to proteoglycans has been on the synthesis of glycosaminoglycan oligosaccharides 39–4445–68 and the tetrasaccharide linker. 69–79 Recently, we have begun to develop a strategy towards the proteoglycan family glycopeptides with syndecan-3 as the target.…”

Section: Introductionmentioning

confidence: 99%

Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains

Yang

Yoshida

Yang

et al. 2016

Carbohydrate Research

Self Cite

View full text Add to dashboard Cite

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 of the synthesis of syndecan-3 glycopeptide (53–62) containing two different heparan sulfate chains. For assembly of glycans, a convergent 3+2+3 approach was developed producing two different octasaccharide amino acid cassettes, which were utilized towards syndecan-3 glycopeptides. The glycopeptides presented many obstacles for post-glycosylation manipulation, peptide elongation, and deprotection. Following screening of multiple synthetic sequences, a successful strategy was finally established by constructing partially deprotected single glycan chain containing glycopeptides first, followed by coupling of the glycan-bearing fragments and cleavage of the acyl protecting groups.

show abstract

Strategies in Synthesis of Heparin/Heparan Sulfate Oligosaccharides

Cited by 82 publications

References 125 publications

Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers

Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers

Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity

Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains

Contact Info

Product

Resources

About