Table 2. I10H Analogues Synthetic Yields and Their KLK5 Inhibition.
| Analogues | Sequence a | Molecular Weight | Isolated yield from linear precursor /% | Boc-VPR-AMC IC50 (N = 3)/nM b | Inhibitory Constant (Ki)/nM |
|---|---|---|---|---|---|
| I10H | GRCTKSIPPHCFPD | 1537.8 (calculated) 1538.3 (measured) | 19 | 352 ±144 | 322 |
| 1 (K5R_I10H) | GRCTRSIPPHCFPD | 1565.8 (calculated) 1566.2 (measured) | 24 | 65 ±10 | 60 |
| 2 (I10H_F12W) | GRCTKSIPPHCWPD | 1576.8 (calculated) 1577.2 (measured) | 25 | 36 ±15 | 33 |
| 3 (G1N_I10H) | NRCTKSIPPHCFPD | 1594.8 (calculated) 1595.2 (measured) | 25 | 511 ±86 | 467 |
| 4 (I10H_F12Y) | GRCTKSIPPHCYPD | 1553.8 (calculated) 1554.1 (measured) | 19 | 334 ±31 | 305 |
| 5 (I7K_I10H) | GRCTKSKPPHCFPD | 1552.8 (calculated) 1553.2 (measured) | 16 c | >10,000 | >9000 |
a Letters in bold indicate the additional substitution made to I10H.
b IC50 curves of each tested ligand are displayed in S2 Fig.
c reduced yield due to repeated purification.