M

Chlorovaleryl Chloride
Figure 27 Alternative route to the synthesis of compound 59.

Figure 28 Synthesis of polylactose 71, with a lactose/acrylamide ratio of 1:2.5, as a control for bioassays. Reagents: (a) PtO2, H2, MeOH, then 2.5-chlorovaleryl chloride, Et3N, 79%; (b) NaN3, DMF, 70°C, 84%; (c) NaOMe, MeOH; (d) PtO2/H2, H2O-MeOH, 91% (two steps); (e) pNAS, DMF, rt, 24 h; 65°C, 6h; rt, 24 h, then NH'HO, 24 h.

Figure 28 Synthesis of polylactose 71, with a lactose/acrylamide ratio of 1:2.5, as a control for bioassays. Reagents: (a) PtO2, H2, MeOH, then 2.5-chlorovaleryl chloride, Et3N, 79%; (b) NaN3, DMF, 70°C, 84%; (c) NaOMe, MeOH; (d) PtO2/H2, H2O-MeOH, 91% (two steps); (e) pNAS, DMF, rt, 24 h; 65°C, 6h; rt, 24 h, then NH'HO, 24 h.

Galp-(1^4)-^-d-GlcNAc 11 in all cases. The efficacy can be illustrated by the IC50 result for polymer 60C of 5.6 nM, which is 5.0 x 104-fold better than its trisaccharide analog 11 in inhibiting anti-Gal IgA. The enhancement proved to be greater for anti-Gal IgM and IgA than for anti-Gal IgG. For example, the activity enhancement of polymer 60B was 246-, 1.0 x 104-, and 4.4 x 104-fold better toward anti-Gal IgG, IgA, and IgM, respectively. This observation is consistent with the increasing numbers of binding sites from IgG to IgA to IgM. In human serum, IgM exists as a pentamer with 10 equivalent binding sites in one molecule; 80% of IgA exists as a monomer with two binding sites and 20% as higher order oligomers with multiple binding sites; IgG exists as a monomer with two binding sites. Therefore, a "mul-

Table 3 Inhibition of a-gal Polymers and Monomer Against the Binding of Purified Human anti-Gal Antibody (male, blood type: AB) to Mouse Laminin

Table 3 Inhibition of a-gal Polymers and Monomer Against the Binding of Purified Human anti-Gal Antibody (male, blood type: AB) to Mouse Laminin

Compound

Ratioa

IgG

IgA

IgM

Monomer 11

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