Table 2.
SFTI-1 and its synthetic analogs, their inhibitory activities, and PDB codes (if available) of their crystal and/or solution structures. Modified positions are marked in bold. The cyclization is indicated by (&), according to the recommendation of Spengler et al. [90].
| SFTI-1 from Helianthus annuus and Its Synthetic Analogs | |
|---|---|
| Name (If Given) and Sequence | Ki (nM) (Enzyme) (Structure in PDB, If Reported) |
|
Bicyclic(native) SFTI-1 &1GRC(&2)TKSIPPIC(&2)FPD&1 |
0.1 (trypsin) [49] (crystal structure 1SFI [49], 1JBL solution structure [91]); 102 (matriptase) (crystal structure with matriptase catalytic domain 3P8F [92]); 218 (matriptase-2) [93]; 0.15 (cathepsin G); 105,000 (elastase); 7400 (chymotrypsin); 136,000 (thrombin) [49]; 143 (KLK5); 25.1 (KLK14) [94]; 4960 (mesotrypsin) [95] |
|
Monocyclic SFTI-1 GRC(&)TKSIPPIC(&)FPD |
0.02698 (trypsin) [96] (solution structure 1JBN [91]);703 (matriptase) [97]; 61 (matriptase); 1365 (matriptase-2) [93]; 26,980 (20S proteasome, ChT-L); 29,090 (20S proteasome, C-L) [98] |
| GRC(&)TKSIAPIC(&)FPD | 27 (matriptase); 0.035 (trypsin) [99] |
| GRC(&)TKSIPAIC(&)FPD | 370 (matriptase); 0.0017 (trypsin) [99] |
| GRC(&)TKSIPPIC(&)FAD | 240 (matriptase); 0.0037 (trypsin) [99] |
| GRC(&)TKSIPPIC(&)FPA | 1500 (matriptase); 0.01 (trypsin) [99] |
| &1GRC(&2)TRSIPPIC(&2)FPD&1 | 19 (matriptase-2); 269 (matriptase); 13.4 (trypsin) [93] |
| GRC(&)TRSIPPIC(&)FPD | 91 (matriptase); 115 (matriptase-2); 15.2 (trypsin) [93] |
| GRC(&)TFSIPPIC(&)FPD | 0.5 (chymotrypsin) [100] |
| GRC(&)TXSIPPIC(&)FPD X = 4-fluoro-l-phenylalanine |
0.03 (chymotrypsin) [101] (Ki calculated as a reciprocal value of originally published Ka 3.0 × 1010 M−1) |
| GRC(&)TVSIPPIC(&)FPD | 71 (neutrophil elastase) [102] |
| GRC(&)TKSIPPRC(&)FPD | 6.4 (matriptase); 0.0038 (trypsin) [99] |
| GRC(&)TKSIPPKC(&)FPD | 40 (matriptase); 0.0057 (trypsin) [99] |
| GKC(&)TKSIPPIC(&)FPD | 1200 (matriptase); 0.002 (trypsin) [99] |
| GRC(&)TRSIPXIC(&)FPD X = Abu (aminobutyric acid) |
0.5 (trypsin) [100] |
| &1GrC(&2)TRSIPPIC(&2)FPD&1 r = d-Arg |
280 (matriptase-2); 63,360 (matriptase) [93] |
| GrC(&)TRSIPPIC(&)FPD r = d-Arg |
433 (matriptase-2); 76,310 (matriptase) [93] |
| &1KRC(&2)TRSIPPIC(&2)FPD&1 | 127 (matriptase-2); 532 (matriptase) [103] |
| &1GRC(&2)TKSIPPRC(&2)HPD&1 | 3.6 (matriptase) [97] |
|
SDMI-1 GRC(&)TKSIPPRC(&)HPD |
11.2 (matriptase) [97] |
|
SDMI-3 KRC(&)TKSIPPRC(&)HPD |
2.1 (matriptase) [97] |
| &1KRC(&2)TKSIPPRC(&2)HPD&1 | 4.1 (matriptase) [97] |
| K(&1)RC(&2)TKSIPPRC(&2)HPD&1 | 4.1 (matriptase) [97] |
| K(&1)RC(&2)TKSIPPRC(&2)HP&1 | 7.2 (matriptase) [97] |
| K(&1)RC(&2)TKSIPPRC(&2)H&1 | 2.6 (matriptase) [97] |
| &1GRC(&2)TRSIPPRC(&2)HPD&1 | 15 (matriptase-2); 4.9 (matriptase) [103] |
| GRC(&)TRSIPPRC(&)HPD | 127 (matriptase-2); 532 (matriptase) [103] |
| &1KRC(&2)TRSIPPRC(&2)HPD&1 | 102 (matriptase-2); 8.3 (matriptase); 9 (trypsin) [103] |
| K(&1)RC(&2)TRSIPPRC(&2)HPD&1 | 257 (matriptase-2); 2.6 (matriptase); 5.1 (trypsin) [103] |
| KRC(&)TRSIPPRC(&)HPD | 318 (matriptase-2); 4.3 (matriptase); 5.3 (trypsin) [103] |
| &1GRC(&2)TRSIPPHC(&2)WPD&1 | 51 (KLK5) [104] |
| &1GRC(&2)TRSYPPIC(&2)FPD&1 | 214 (thrombin) [105] |
| GVC(&)TLSIPPIC(&)FPD | 300 (pancreatic elastase) [106] |
| &1GRC(&2)YKSKPPIC(&2)FPD&1 | 0.05 (plasmin, crystal structure 6D3X); 160 (trypsin); 29,000 (cathepsin G) [107] |
| &1GRC(&2)QXSEPPEC(&2)FPD&1 X= 4-chloro-l-phenylalanine |
1.8 (chymase); 330 (chymotrypsin); 150 (cathepsin G) [108] |
| &1GTC(&2) X1
X2SDPPIC(&2)FPN&1 X1 = norleucine; X2 = 4-guanidine-l-phenylalanine |
1.6 (cathepsin G) [109] |
| GRC(&)TXSIPPIC(&)FPD X = 4-guanidine-l-phenylalanine |
5.55 (chymotrypsin) [101] (Ki calculated as a reciprocal value of originally published Ka 1.8 108 M−1) |
| KRC(&)KKSIPPRC(&)HPD | 3.8 (furin) [110] |
| KRC(&)KKSIPPRC(&)F-NH2 | 0.49 (furin) [110] |
| &1GFC(&2)QRSIPPIC(&2)FPD&1 | 3.59 (KLK4 [111], crystal structure 4K1E [112]) |
| &1GFC(&2)QRSIPPIC(&2)FPN&1 | 0.04 (KLK4 [90], crystal structure 4KEL [113]) |
| &1GYC(&2)NRSYPPEC(&2)FPN&1 | 0.34 (KLK5); 18 (KLK14) [114] |
| &1GFC(&2)HRSYPPEC(&2)WPN&1 | 2.4 (KLK5, solution structure 6NOX) [114] 150 (KLK14) [114] |
| &1GKC(&2)LFSNPPIC(&2)FPN&1 | 0.14 (KLK7); 170 (chymotrypsin) [115] |
| &1GWC(&2)IRSKPPIC(&2)NPN&1 | 7.0 (KLK14); 19.9 (KLK4); 3200 (trypsin) [105] |
|
SFMI-1 GIC(&)SRSLPPIC(&)IPD |
65 (MASP-1); 1030 (MASP-2); 260 (trypsin) [116] |
|
SFMI-2 GYC(&)SRSYPPVC(&)IPD |
180 (MASP-2); 1000 (trypsin) [116] |
| GRC(&)TRSXPPIC(&)FPD X = 4,4′-biphenyl-l-alanine |
28 (mesotrypsin) [117] |
| &1GX1C(&2)YX2SYPPIC(&2)NPN&1 X1 = 4,4′-biphenyl-l-alanine; X2 = norvaline |
6.1 (proteinase 3); 16 (neutrophil elastase) [118] |
| &1GTC(&2)YXSYPPIC(&2)NPN&1X = Abu | 7.0 (proteinase 3); 3.2 (neutrophil elastase) [118] |
| GRC(&)TRSKKPIC(&)FPD | 310 (20S proteasome, ChT-L); 20,140 (20S proteasome, T-L); 680 (20S proteasome, C-L) [96] |
| &1GTC(&2)TRSIPPIC(&2)NPN&1 | 0.71 (trypsin [94], crystal structure 6BVH [119]) |
|
RXC(&)TRSKKPIC(&)FPD X = N-arginine (peptoid monomer) |
80 (20S proteasome, ChT-L); 14,000 (20S proteasome, T-L); 140 (20S proteasome, C-L) [98] |
| O2Oc-GRC(&)TRSKKPIC(&)FPD | 310 (20S proteasome, ChT-L); 1150 (20S proteasome, T-L); 350 (20S proteasome, C-L) [98] |
| RGC(&1)TRSKKPIC(&2)GPGGGC(&2)TR--SKKPIC(&1)FPD | 30 (20S proteasome, ChT-L); 20 (20S proteasome, C-L) [98] |
SFTI-1—Sunflower trypsin inhibitor 1; SDMI—SFTI-1 derived matriptase inhibitor -1; SFMI- sunflower mannose-binding lectin-associated serine protease inhibitor; ChT-L—chymotrypsin-like activity; C-L—caspase-like activity; T-L—trypsin-like activity; KLK—kallikrein; MASP-1—mannan-binding lectin serine protease 1; MASP-2—mannan-binding lectin serine protease 2; Abu-aminobutyric acid; O2Oc—8-amino-3,6-dioxaoctanoyl group.