Nickel‐Catalyzed Stereoselective Formation of 1,2‐<b><i>cis</i></b>‐2‐Aminoglycosides

Sletten, Eric T.; Loka, Ravi S.; Fairweather, Alisa E.R.; Nguyen, Hien M.

doi:10.1002/9783527696239.ch9

Cited by 1 publication

(3 citation statements)

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“…Surprisingly, both HS heptasaccharide 69 (IC 50 = 41.68 ± 3.64 μM, Scheme 10) and octasaccharide 70 (IC 50 = 3.94 ± 0.20 μM, Scheme 10) exhibited significantly decreased binding to heparanase compared to 1α. 33 The low potency compound 69 is similar in activity to trisaccharide 1β (Table 4, entry 2) bearing the βconfigured reducing end. Although octasaccharide 70 is more potent than 69, its potency is approximately 10-fold lower than that of trisaccharide 1α (Table 4, entry 1).…”

Section: Interaction Of the Hs Trisaccharides With Heparanasementioning

confidence: 93%

“…: In the docking study, the enzyme structure was inherited from previously modified apo heparanase structure (PDB code: 5E8M). 11,33 The ligand saccharide backbone was obtained from Glycam GAGs builders (www.glycam.com), then the sulfation patterns and aliphatic portion was modified on GaussView 5.0. 61 The modified ligand pdb files were then subjected to energy minimization in YASARA, and saved in .yob format.…”

Section: General Procedures For Global Deprotection-mentioning

confidence: 99%

“…The excluded volume (Vo) is marked by blue dextran and the total included volume (Vt) by phenol red. Degradation fragments of HS side chains, characterized as previously described, 50 are eluted from Sepharose 6B at 0.5 < Kav < 0.8 (fractions [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. Results are best represented by the actual gel filtration pattern.…”

Section: K D Determination Using Platelet Factor 4 Binding Test By Biolayer Interferometrymentioning

confidence: 99%

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Modulating Heparanase Activity: Tuning Sulfation Pattern and Glycosidic Linkage of Oligosaccharides

Zhu

Loka

et al. 2020

J. Med. Chem.

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Heparanase cleaves polymeric heparan sulfate (HS) molecules into smaller oligosaccharides, allowing for release of angiogenic growth factors promoting tumor development and autoreactive immune cells to reach the insulin-producing β cells. Interaction of heparanase with HS chains is regulated by specific substrate sulfation sequences. We have synthesized eleven trisaccharides that are highly tunable in structure and sulfation pattern, allowing us to determine how heparanase recognizes HS substrate and selects a favorable cleavage site. Our study shows that ( 1) N-SO 3 − at +1 subsite and 6-O-SO 3 − at −2 subsite of trisaccharides are critical for heparanase recognition; (2) addition of 2-O-SO 3 − at the −1 subsite and of 3-O-SO 3 − to GlcN unit is not advantageous; and (3) the anomeric configuration (α or β) at the reducing end is crucial in controlling heparanase activity. Our study also illustrates that the α-trisaccharide having Nand 6-O-SO 3 − at −2 and +1subsites inhibited heparanase and was resistant toward hydrolysis.

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Section: Interaction Of the Hs Trisaccharides With Heparanasementioning

confidence: 93%

Section: General Procedures For Global Deprotection-mentioning

confidence: 99%