Table 1.
Analytical characterization of the inhibitors and their potency against furin. Abbreviations of unusual residues are shown below the table.
| No. | Sequence | HPLC (min) | MS calc. | MS found (M+H)+ | Furin Ki (pM)[c] | R2[d] |
|---|---|---|---|---|---|---|
| 4 | Phac-Arg-Arg-Val-Arg-4-Amba | 23.1 | 834.51 | 835.33 | 56.3 ± 7.7[b] | 0.996 |
| 5 | Phac-Arg-Arg-Arg-Val-Arg-4-Amba | 22.5 | 990.61 | 496.27[a] | 13.8 ± 4.5[b] | 0.993 |
| 6 | Phac-Arg-Ala-Arg-Val-Arg-4-Amba | 21.6 | 905.55 | 906.54 | 45.9 ± 12.5[b] | 0.998 |
| 7 | Phac-Ala-Arg-Arg-Val-Arg-4-Amba | 23.8 | 905.55 | 453.73[a] | 49.1 ± 19.2[b] | 0.997 |
|
| ||||||
| 8 | H-Arg-Arg-Arg-Val-Arg-4-Amba | 15.9 | 872.57 | 437.29[a] | 33.7 ± 1.3[b] | 0.987 |
| 9 | H-DArg-Arg-Arg-Val-Arg-4-Amba | 16.3 | 872.57 | 873.43 | 28.3 ± 9.7[b] | 0.991 |
| 10 | H-DArg-DArg-Arg-Val-Arg-4-Amba | 15.5 | 872.57 | 873.53 | 51.0 ± 6.7[b] | 0.988 |
| 11 | H-DArg-DArg-DArg-Arg-Val-Arg-4-Amba | 16.5 | 1028.67 | 1029.66 | 75.4 ± 10.6[b] | 0.987 |
| 12 | H-DArg-DArg-DArg-DArg-Arg-Val-Arg-4-Amba | 17.1 | 1184.77 | 593.53[a] | 94.3 ± 24.3[b] | 0.979 |
| 13 | H-DArg-Arg-Val-Arg-4-Amba | 15.8 | 716.47 | 359.37[a] | 108 ± 61[b] | 0.967 |
| 14 | H-Arg-Arg-Val-Arg-4-Amba | 15.6 | 716.47 | 359.37[a] | 110 ± 10[b] | 0.974 |
| 15 | H-DArg-Arg-Tle-Arg-4-Amba | 17.1 | 730.48 | 366.39[a] | 37.8 ± 19.5[b] | 0.981 |
| 16 | N(Ca)Arg-Arg-Arg-Val-Arg-4-Amba | 17.0 | 914.59 | 458.38[a] | 6.2 ± 1.0[b] | 0.993 |
| 17 | N(Ca)Arg-Ala-Arg-Val-Arg-4-Amba | 16.8 | 829.53 | 415.87[a] | 11.9 ± 3.4[b] | 0.996 |
|
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| 18 | Ac-Leu-Leu-Leu-Leu-Arg-Val-Lys-4-Amba | 38.1 | 1026.71 | 1027.80 | 491 ± 70 | |
| 19 | Ac-DLeu-Leu-Leu-Leu-Arg-Val-Lys-4-Amba | 40.1 | 1026.71 | 514.74[a] | 449 ± 34 | |
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| 20 | Ac-Leu-Leu-Leu-Leu-Arg-Tle-Lys-4-Amba | 38.7 | 1040.72 | 1041.95 | 193 ± 33 | |
| 21 | Ac-Leu-Leu-Leu-Leu-Arg-Val-Arg-4-Amba | 38.6 | 1054.71 | 1055.8 | 164 ± 21[b] | 0.996 |
| 22 | Ac-Leu-Leu-Leu-Leu-Arg-Tle-Arg-4-Amba | 39.5 | 1068.73 | 1069.8 | 78.6 ± 8.4[b] | 0.998 |
|
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| 23 | 3-AMe-Phac-Val-Arg-4-Amba | 19.3 | 551.33 | 552.40 | 48 200 ± 13 600 | |
| 24 | 4-AMe-Phac-Val-Arg-4-Amba | 18.6 | 551.33 | 552.30 | 37 800 ± 12 800 | |
| 25 | 3-GMe-Phac-Val-Arg-4-Amba | 20.8 | 593.36 | 594.30 | 164 000 ± 21 200 | |
| 26 | 4-GMe-Phac-Val-Arg-4-Amba | 20.1 | 593.36 | 594.20 | 269 300 ± 25 600 | |
| 27 | 5-Ava-Val-Arg-4-Amba | 16.0 | 503.33 | 504.10 | 38 500 ± 2 900 | |
| 28 | 5-Gva-Val-Arg-4-Amba | 17.7 | 545.36 | 546.33 | 2 500 ± 300 | |
| 29 | 5-Ava-Tle-Arg-4-Amba | 17.6 | 517.35 | 518.15 | 26 700 ± 900 | |
| 30 | 5-Gva-Tle-Arg-4-Amba | 19.3 | 559.37 | 560.24 | 1 260±100 | |
[a]
(M + 2H)2+/2
[b]
Ki values were determined under tight-binding conditions (for inhibitors with Ki values < 170 pM).
[c]
Data represent the mean ± SD obtained by at least three independent measurements.
[d]
Coefficient of determination
Used abbreviations: Ac, acetyl; AMe-Phac, aminomethyl-phenylacetyl; 5-Ava, 5-aminovaleroyl; N(Ca)Arg, Nα(carbamidoyl)-arginine; GMe-Phac, guanidinomethyl-phenylacetyl; Gva, 5-guanidinovaleroyl; Phac, phenylacetyl; Tle, tert.leucine or tert.butylglycine.