Thrombolytic potency of PEGylated SakSTAR variants after bolus injection in a hamster pulmonary embolism model
| Compound . | Dose (μg/kg) . | n . | Lysis at 90 min (%) . | Isotope Recovery (%) . | Residual Fg4-150 (%) . | Residual α2antiplasmin (%) . | Sak-related Antigen After 90 min (ng/mL) . | C50 (μg/kg) . |
|---|---|---|---|---|---|---|---|---|
| Saline | — | 9 | 20 ± 3 | 96 ± 2 | 110 ± 6 | 120 ± 6 | — | — |
| SakSTAR | 27 | 5 | 34 ± 6 | 89 ± 6 | 120 ± 12 | 140 ± 7 | 1 ± 0 | |
| 81 | 5 | 44 ± 10 | 86 ± 5 | 140 ± 39 | 130 ± 8 | 1 ± 0 | 110 | |
| 240 | 4 | 85 ± 4 | 74 ± 2 | 130 ± 20 | 100 ± 7 | 11 ± 1 | ||
| SakSTAR(K96C-SP5) | 27 | 4 | 36 ± 5 | 100 ± 3 | 110 ± 8 | 100 ± 1 | 2 ± 0 | |
| 81 | 4 | 58 ± 8 | 94 ± 3 | 110 ± 7 | 110 ± 2 | 9 ± 1 | 65 | |
| 240 | 4 | 86 ± 4 | 100 ± 1 | 110 ± 4 | 100 ± 3 | 27 ± 2 | ||
| SakSTAR(K102C-SP5) | 27 | 4 | 42 ± 4 | 97 ± 3 | 110 ± 2 | 110 ± 4 | 3 ± 0 | |
| 81 | 4 | 68 ± 4 | 100 ± 5 | 100 ± 5 | 110 ± 3 | 9 ± 1 | 50 | |
| 240 | 4 | 88 ± 3 | 82 ± 2 | 99 ± 4 | 100 ± 3 | 40 ± 4 | ||
| SakSTAR(K109C-SP5) | 27 | 4 | 43 ± 5 | 88 ± 6 | 110 ± 6 | 140 ± 3 | 2 ± 0 | |
| 81 | 4 | 64 ± 5 | 80 ± 2 | 120 ± 7 | 130 ± 16 | 9 ± 3 | 53 | |
| 240 | 4 | 86 ± 5 | 84 ± 3 | 120 ± 10 | 120 ± 12 | 39 ± 7 | ||
| SakSTAR(K135C-SP5) | 27 | 4 | 19 ± 3 | 100 ± 2 | 120 | 120 ± 8 | 5 ± 2 | |
| 81 | 4 | 38 ± 12 | 99 ± 4 | 120 ± 11 | 110 ± 3 | 9 ± 1 | 110 | |
| 240 | 4 | 79 ± 4 | 93 ± 1 | 120 ± 14 | 100 ± 2 | 46 ± 6 | ||
| SakSTAR(K96C-SP5, K135C-SP5) | 9 | 4 | 25 ± 1 | 94 ± 2 | 120 ± 6 | 150 ± 9 | 8 ± 1 | |
| 27 | 4 | 50 ± 6 | 90 ± 1 | 97 ± 5 | 130 ± 11 | 25 ± 5 | 30 | |
| 81 | 4 | 83 ± 4 | 77 ± 1 | 99 ± 3 | 120 ± 7 | 82 ± 15 | ||
| SakSTAR(S3C-SP5) | 9 | 4 | 28 ± 4 | 100 ± 2 | 210 ± 44 | 120 ± 12 | 0 | |
| 27 | 4 | 53 ± 10 | 88 ± 8 | 180 ± 19 | 130 ± 9 | 1 ± 0 | 21 | |
| 81 | 4 | 75 ± 8 | 86 ± 2 | 130 ± 25 | 100 ± 3 | 3 ± 0 | ||
| SakSTAR(2SC-SP5, S3C-SP5) | 3 | 4 | 26 ± 2 | 97 ± 2 | 180 ± 34 | 100 ± 3 | 0 | |
| 9 | 4 | 62 ± 5 | 90 ± 2 | 130 ± 8 | 93 ± 9 | 1 ± 0 | 6 | |
| 27 | 4 | 79 ± 8 | 85 ± 2 | 110 ± 23 | 92 ± 5 | 6 ± 1 | ||
| SakSTAR(S3C-MP5) | 9 | 4 | 24 ± 5 | 99 ± 2 | 130 ± 13 | 100 ± 4 | 1 ± 0 | |
| 27 | 4 | 55 ± 3 | 83 ± 3 | 120 ± 12 | 100 ± 5 | 2 ± 0 | 24 | |
| 81 | 4 | 85 ± 5 | 84 ± 4 | 110 ± 16 | 100 ± 8 | 13 ± 2 | ||
| SakSTAR(S3C-MP10) | 9 | 4 | 35 ± 3 | 99 ± 3 | 130 ± 13 | 110 ± 4 | 7 ± 0 | |
| 27 | 4 | 75 ± 2 | 96 ± 1 | 130 ± 16 | 110 ± 5 | 21 ± 2 | 17 | |
| 81 | 4 | 91 ± 1 | 71 ± 3 | 140 ± 20 | 110 ± 2 | 180 ± 50 | ||
| SakSTAR(S3C-MP20) | 3 | 4 | 36 ± 2 | 92 ± 4 | 150 ± 32 | 110 ± 2 | 9 ± 1 | |
| 9 | 4 | 52 ± 8 | 90 ± 5 | 130 ± 20 | 110 ± 3 | 43 ± 5 | 7 | |
| 27 | 4 | 81 ± 4 | 82 ± 4 | 140 ± 29 | 110 ± 3 | 160 ± 14 |
| Compound . | Dose (μg/kg) . | n . | Lysis at 90 min (%) . | Isotope Recovery (%) . | Residual Fg4-150 (%) . | Residual α2antiplasmin (%) . | Sak-related Antigen After 90 min (ng/mL) . | C50 (μg/kg) . |
|---|---|---|---|---|---|---|---|---|
| Saline | — | 9 | 20 ± 3 | 96 ± 2 | 110 ± 6 | 120 ± 6 | — | — |
| SakSTAR | 27 | 5 | 34 ± 6 | 89 ± 6 | 120 ± 12 | 140 ± 7 | 1 ± 0 | |
| 81 | 5 | 44 ± 10 | 86 ± 5 | 140 ± 39 | 130 ± 8 | 1 ± 0 | 110 | |
| 240 | 4 | 85 ± 4 | 74 ± 2 | 130 ± 20 | 100 ± 7 | 11 ± 1 | ||
| SakSTAR(K96C-SP5) | 27 | 4 | 36 ± 5 | 100 ± 3 | 110 ± 8 | 100 ± 1 | 2 ± 0 | |
| 81 | 4 | 58 ± 8 | 94 ± 3 | 110 ± 7 | 110 ± 2 | 9 ± 1 | 65 | |
| 240 | 4 | 86 ± 4 | 100 ± 1 | 110 ± 4 | 100 ± 3 | 27 ± 2 | ||
| SakSTAR(K102C-SP5) | 27 | 4 | 42 ± 4 | 97 ± 3 | 110 ± 2 | 110 ± 4 | 3 ± 0 | |
| 81 | 4 | 68 ± 4 | 100 ± 5 | 100 ± 5 | 110 ± 3 | 9 ± 1 | 50 | |
| 240 | 4 | 88 ± 3 | 82 ± 2 | 99 ± 4 | 100 ± 3 | 40 ± 4 | ||
| SakSTAR(K109C-SP5) | 27 | 4 | 43 ± 5 | 88 ± 6 | 110 ± 6 | 140 ± 3 | 2 ± 0 | |
| 81 | 4 | 64 ± 5 | 80 ± 2 | 120 ± 7 | 130 ± 16 | 9 ± 3 | 53 | |
| 240 | 4 | 86 ± 5 | 84 ± 3 | 120 ± 10 | 120 ± 12 | 39 ± 7 | ||
| SakSTAR(K135C-SP5) | 27 | 4 | 19 ± 3 | 100 ± 2 | 120 | 120 ± 8 | 5 ± 2 | |
| 81 | 4 | 38 ± 12 | 99 ± 4 | 120 ± 11 | 110 ± 3 | 9 ± 1 | 110 | |
| 240 | 4 | 79 ± 4 | 93 ± 1 | 120 ± 14 | 100 ± 2 | 46 ± 6 | ||
| SakSTAR(K96C-SP5, K135C-SP5) | 9 | 4 | 25 ± 1 | 94 ± 2 | 120 ± 6 | 150 ± 9 | 8 ± 1 | |
| 27 | 4 | 50 ± 6 | 90 ± 1 | 97 ± 5 | 130 ± 11 | 25 ± 5 | 30 | |
| 81 | 4 | 83 ± 4 | 77 ± 1 | 99 ± 3 | 120 ± 7 | 82 ± 15 | ||
| SakSTAR(S3C-SP5) | 9 | 4 | 28 ± 4 | 100 ± 2 | 210 ± 44 | 120 ± 12 | 0 | |
| 27 | 4 | 53 ± 10 | 88 ± 8 | 180 ± 19 | 130 ± 9 | 1 ± 0 | 21 | |
| 81 | 4 | 75 ± 8 | 86 ± 2 | 130 ± 25 | 100 ± 3 | 3 ± 0 | ||
| SakSTAR(2SC-SP5, S3C-SP5) | 3 | 4 | 26 ± 2 | 97 ± 2 | 180 ± 34 | 100 ± 3 | 0 | |
| 9 | 4 | 62 ± 5 | 90 ± 2 | 130 ± 8 | 93 ± 9 | 1 ± 0 | 6 | |
| 27 | 4 | 79 ± 8 | 85 ± 2 | 110 ± 23 | 92 ± 5 | 6 ± 1 | ||
| SakSTAR(S3C-MP5) | 9 | 4 | 24 ± 5 | 99 ± 2 | 130 ± 13 | 100 ± 4 | 1 ± 0 | |
| 27 | 4 | 55 ± 3 | 83 ± 3 | 120 ± 12 | 100 ± 5 | 2 ± 0 | 24 | |
| 81 | 4 | 85 ± 5 | 84 ± 4 | 110 ± 16 | 100 ± 8 | 13 ± 2 | ||
| SakSTAR(S3C-MP10) | 9 | 4 | 35 ± 3 | 99 ± 3 | 130 ± 13 | 110 ± 4 | 7 ± 0 | |
| 27 | 4 | 75 ± 2 | 96 ± 1 | 130 ± 16 | 110 ± 5 | 21 ± 2 | 17 | |
| 81 | 4 | 91 ± 1 | 71 ± 3 | 140 ± 20 | 110 ± 2 | 180 ± 50 | ||
| SakSTAR(S3C-MP20) | 3 | 4 | 36 ± 2 | 92 ± 4 | 150 ± 32 | 110 ± 2 | 9 ± 1 | |
| 9 | 4 | 52 ± 8 | 90 ± 5 | 130 ± 20 | 110 ± 3 | 43 ± 5 | 7 | |
| 27 | 4 | 81 ± 4 | 82 ± 4 | 140 ± 29 | 110 ± 3 | 160 ± 14 |
Data represent mean ± SEM of n experiments.
Fg indicates fibrinogen.