TABLE 2.
Effect of de-2, -6, or -N sulfation (with and without re-N-Ac) on inhibitory activity of heparin against merozoite invasion in growth inhibition assaysa
| Modification | Parent compound | % inhibition (SEM) |
Loss of inhibition (%) | |
|---|---|---|---|---|
| Parent compound | Modified compound | |||
| De-2-Sb | MH | 68 (7) | 26 (2) | 42c |
| MH gc | 77 (9) | 54 (6) | 23 | |
| LH | 74 (7) | 49 (0) | 25 | |
| MH of 5 kDa | 75 (6) | 45 (4) | 30 | |
| MH of 5 kDa gc | 73 (8) | 41 (1) | 32 | |
| MH H2O2 gc | 62 (4) | 7 (1) | 55c | |
| MH of 3 kDa | 37 (0) | 15 (4) | 22c | |
| MH of 3 kDa gc | 70 (8) | 11 (5) | 59c | |
| De-6-S | MH | 68 (7) | 5 (1) | 63c |
| MH gc | 77 (9) | 61 (6) | 16 | |
| MH gc de-2-S | 54 (6) | 21 (1) | 33c | |
| MH of 5 kDa | 75 (6) | 41 (4) | 34c | |
| De-NS (NH)b | MH gc | 77 (9) | 17 (4) | 60c |
| Partially N-Acb | MH gc | 77 (9) | 62 (6) | 15 |
| MH of 5 kDa gc | 73 (8) | 64 (2) | 9 | |
| MH H2O2 | 57 (4) | 15 (3) | 42c | |
| MH H2O2 gc de-2-S | 7 (1) | 3 (1) | 4 | |
| MH gc de-2-s | 54 (6) | 24 (8) | 30 | |
| MH de-2-S | 26 (2) | 28 (3) | −2 | |
| LH de-2-S | 49 (0) | 8 (6) | 41c | |
| Totally N-Ac | MH | 68 (7) | 47 (4) | 21 |
| MH de-2-S | 26 (2) | 23 (2) | 3 | |
| MH gc | 77 (9) | 8 (3) | 69c | |
| MH gc de-2-S | 54 (6) | 0 (3) | 54c | |
| LH de-2-S | 49 (0) | −8 (6) | 57c | |
Modified heparin compounds at 100 μg/ml each were tested for inhibition of P. falciparum in growth inhibition assays. Comparisons of parent and desulfated modified compounds were made. In the majority of cases, desulfation resulted in a reduction of inhibitory activity. The loss of inhibitory activity was calculated as (percent inhibition of the parent compound − percent inhibition of the modified compound). Positive values indicate reduced inhibitory activity of the modified compound compared to that of the parent compound. Negative values indicate increased inhibitory activity of the modified compound compared to that of the parent compound. Data are mean inhibition ± SEM from two assays performed in duplicate. Abbreviations: MH, mucosal heparin (porcine); LH, lung heparin (bovine); gc, glycol splitting; NS, nonsulfated; N-Ac, N-acetylated.
Significant difference of modification across groups of modified compounds.
Significant differences in inhibitory activity between the parent and modified compounds (P > 0.05, corrected for multiple comparisons by the Holm-Sidak method).