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. 2008 Mar 12;130(10):2959-61.
doi: 10.1021/ja709993p. Epub 2008 Feb 15.

Neuroactive chondroitin sulfate glycomimetics

Manish Rawat  1 , Cristal I Gama, John B Matson, Linda C Hsieh-Wilson
Affiliations

Neuroactive chondroitin sulfate glycomimetics

Manish Rawat et al. J Am Chem Soc. .
No abstract available

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Figures

Figure 1
Figure 1
Schematic representation of (A) natural CS and (B) CS glycopolymers. Grey and white circles represent the monosaccharide subunits, red circles represent sulfation.
Figure 2
Figure 2
CS-E glycopolymers inhibit the outgrowth of hippocampal neurons. (A) Immunofluorescence images of neurons 48 h after treatment with the indicated compound. A fixed glucuronic acid concentration of 0.5 μg/mL was used in each case to examine the effects of multivalency. The molar concentrations were 14.3 nM for the natural CS-E polysaccharide, 12.1 nM for the CS-E tetrasaccharide polymer, and 16.6–53.0 nM for the disaccharide polymers. See Supporting Information for details. (B) Statistical analysis of neurite length. Error bars represent SEM from three separate experiments. P values are relative to the untreated neurons. See Supporting Information for conditions.
Figure 3
Figure 3
Comparison of the inhibitory potencies of CS glycopolymer 16 and the natural polysaccharide at various concentrations. IC50 values are based on the molar concentration of compound required to inhibit neurite outgrowth by 50% relative to untreated neurons. See Supporting Information for details.
Scheme 1
Scheme 1. Synthesis of the Disaccharide Monomera
a Conditions: (a) TMSOTf, CH2Cl2, −20 °C, 69%. (b) HF·pyr, THF/pyr, 25 °C, 95%. (c) AIBN, Bu3SnH, benzene, 50 °C, 92%. (d) DDQ, CH3CN/H2O, 25 °C, 89%. (e) SO3·TMA, DMF, 80 °C, 85%. (f) (i) HF·pyr, THF/pyr, 25 °C; (ii) LiOH, H2O2, then NaOH, MeOH, 25 °C, 89% (two steps).
Scheme 2
Scheme 2. Synthesis of Protected CS Glycopolymers a
a Conditions: (a) 8, 1:5 MeOH/(CH2Cl)2, 55 °C, 24 h. (b) TMSOTf, 4, CH2Cl2, −20 °C, 45%. (c) AIBN, Bu3SnH, benzene, 50 °C, 89%. (d) DDQ, CH3CN/H2O, 25 °C. (e) SO3·TMA, DMF, 80 °C, 71% (two steps).
Scheme 3
Scheme 3. CS Glycomimetics a
a Conditions: (a) (i) HF·pyr, THF/pyr, 25 °C; (ii) LiOH, H2O2, then NaOH, MeOH, 25 °C, 87–97% (two steps).
See this image and copyright information in PMC

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