Table 3.
Inhibitory capacity of heparin-derived and synthetic tetrasaccharides in the Lectin Pathway WieLISA and MASP-mediated C4 deposition assay.
| Tetrasaccharide | Structure | Inhibition (%) in WieLISA | Repeats | Inhibition (%) in C4 assay | Repeats |
|---|---|---|---|---|---|
| BY HEPARINASE I TREATMENT OF (LMW-) HEPARIN | |||||
| Org 32102 | ΔUA2S-GlcNS6S-IdoA2S-GlcNS2S (90%)a | 76 (2) | 3 | 61 (6) | 3 |
| Ron G11237 | ΔUA2S-GlcNS6S-IdoA2S-GlcNS2S (37%) | 81 | 1 | ND | 1 |
| ΔUA2S-GlcNS6S-IdoA2S-AnS1,6an (18%) | |||||
| ΔUA2S-GlcNS6S-IdoA2S-ManNS6S (18%) | |||||
| ΔUA2S-GlcNS6S-GlcA-GlcNS3S6S (8%) | |||||
| ΔUA2S-GlcNS6S-GlcA-GlcNS6S (12%)b | |||||
| SAGAG Peak 1 | ΔUA2S-GlcNS6S + ΔUA2S-GlcNSc | 46 | 1 | 55 | 1 |
| SAGAG Peak 2 | ΔUA2S-GlcNS6S + ΔUA-GlcNS6Sc | 28 | 1 | 47 | 1 |
| SAGAG Peak 3 | ΔUA2S-GlcNS6S + ΔUA2S-GlcNS6Sc | 68 | 1 | 66 | 1 |
| SYNTHETIC TETRASACCHARIDES | |||||
| T7 | IdoA-GlcNAc6S-IdoA-GlcNAc6S-(CH2)5NH2 | 0 | 1 | 0 (0) | 3 |
| T11 | IdoA-GlcNAc6S-IdoA2S-GlcNAc6S-(CH2)5NH2 | 0 | 1 | 0 (0) | 3 |
| T13 | IdoA-GlcNS6S-IdoA-GlcNS6S-(CH2)5NH2 | 0 | 1 | 0 (0) | 3 |
| T38 | IdoA-GlcNS6S-IdoA2S-GlcNS6S-(CH2)5NH2 | 24 | 1 | 10 (10) | 3 |
| T39 | IdoA2S-GlcNAc6S-IdoA2S-GlcNAc6S-(CH2)5NH2 | 0 | 1 | 0 (0) | 3 |
| T40 | IdoA2S-GlcNS6S-IdoA2S-GlcNS6S-(CH2)5NH2 | 30 | 1 | 16 (3) | 3 |
Values are expressed as percentage inhibition compared to control values without inhibitor expressed as mean ± SD or from a single experiment. GAGs were added in a concentration of 100 ug/ml in the LP and C4 assay.
a
Composition and purity by NMR spectroscopy.
b
Composition by NMR spectroscopy.
c
Composition after digestion of the tetrasaccharide with a cocktail of heparinase I, II, and III followed by RPIP-HPLC disaccharide identification.