Table 3.
Modifications to the spacer between the peptide chimera, the Tat potion of the chimeric peptide, and miscellaneous modifications.
| Number | Sequence | RBC Lysis IC50, pH 5.5 (μM) | RBC Lysis IC50, pH 7.4 (μM) |
|---|---|---|---|
| 36a | GLFEAIEGFIENGWEGMIDGWYGCYGRKKRRQRR | 2.09 | 2.1 |
| 36b | CGLFEAIEGFIENGWEGMIDGWYGGGGYGRKKRRQRR | 0.7 | 7.9 |
| 36c | CGLFEAIEGFIENGWEGMIDGWYG(Peg 3)YGRKKRRQRR | 1.92 | >10 |
| 36d | CGLFEAIEGFIENGWEGMIDGWYG(Peg 6)YGRKKRRQRR | 1.22 | >10 |
| 36e | CGLFEAIEGFIENGWEGMIDGWYG(Peg11)YGRKKRRQRR | 2.4 | >100 |
| 36f | CGLFEAIEGFIENGWEGMIDGWYG(Peg 27)YGRKKRRQRR | 28 | >100 |
| 37a | CGLFEAIEGFIENGWEGMIDGWYGYGKKKKKQKK | 7.78 | >100 |
| 37b | CGLFEAIEGFIENGWEGMIDGWYGYGHKKHHQHH | 0.90 ± 0.19 (n = 8) | >100 (n = 8) |
| 37c | CGLFEAIEGFIENGWEGMIDGWYGYGRKKRRQRRR | 1.77 | 6.82 |
| 37d | CGLFEAIEGFIENGWEGMIDGWYGYGRKKRRQR | 0.75 | >100 |
| 37e | CGLFEAIEGFIENGWEGMIDGWYGYGRKKRRQ | 0.96 | >100 |
| 37f | CGLFEAIEGFIENGWEGMIDGWYGYGRKKRR | 1.61 | >100 |
| 37g | CGLFEAIEGFIENGWEGMIDGWYGYGRKKR | 7.8 | >100 |
| 37h | CGLFEAIEGFIENGWEGMIDGWYGYGHKKHHQHR | 0.58 ± 0.17 (n = 10) | >100 (n = 10) |
| 38a | GLFEAIEGFIENGWEGMIDGWYGYGRKKRRQRRC | 0.96 | >10 |
| 38b | YGRKKRRQRRGLFEAIEGFIENGWEGMIDGWYGC | 2.91 | >100 |
| 38c | CYGRKKRRQRRGLFEAIEGFIENGWEGMIDGWYG | 1.17 | >20 |
| 38d | rrqrrkkrgygywgdimgewgneifgeiaeflgc | 5 | >100 |
| 38e | crrqrrkkrgygywgdimgewgneifgeiaeflg | 0.1 | 1.51 |
| 38f | cglfeaiegfiengwegmidgwygygrkkrrqrr | 2.3 | >20 |
All peptides were >95% purity by HPLC analysis and demonstrated the correct HRMS profiles. Peptides were tested three times at each pH unless otherwise noted, and the values are reported as the mean. Standard Deviations are reported for peptides with larger n values to provide a reference for the reproducibility of the data. As solubility allowed, testing at pH 7.4 was pushed to the highest possible concentrations to determine as close as possible approximate IC50.