Table 3. Data Set Used for Testing the Optimized Charges Introduced in Forcefield_NCAAa.
| analog | source | sequence | SeqID | IC50 (μM) |
|---|---|---|---|---|
| 1 | pharmacophore | Ac-ICV(PTR)QDWGAHRCI-NH2 | 28 | 9.60 |
| 2 | pharmacophore | Ac-RCVVQDWGHHRCT-NH2 | 17 | 8.00 |
| 3 | pharmacophore | Ac-LCVVQDWGWHRCG-NH2 | 15 | 5.40 |
| 4 | pharmacophore | Ac-ICVWQDWGWHRCT-NH2 | 24 | 3.10 |
| 5 | pharmacophore | Ac-ICVVNDWGHHRCT-NH2 | 3 | 4.20 |
| 6 | structurekinetic | Ac-ICV(OMY)QDWGAHRCT-NH2 | 5 | 1.30 |
| 7 | pharmacophore | Ac-MCVHQDWGGHRCF-NH2 | 16 | 85.20 |
| 8 | pharmacophore | Ac-ICVWQDWGHHRCT-NH2 | 2 | 2.20 |
| 9 | structurekinetic | Ac-ICV(MTR)QDWGAHRCT-NH2 | 3 | 0.87 |
| 10 | novel analogues | Ac-ICVYQDWGAHRC(NMT)-NH2 | 12 | 1.90 |
| 11 | pharmacophore | Ac-ICV(OMW)QDWGAHRCT-NH2 | 1 | 0.21 |
| 12 | pharmacophore | Ac-ICVSQDWGHHRCT-NH2 | 20 | 50.90 |
| 13 | pharmacophore | Ac-ICVVQDWGHHSCT-NH2 | 10 | 25.00 |
| 14 | pharmacophore | Ac-ICVVQDWGHHRCI-NH2 | 13 | 3.20 |
| 15 | structurekinetic | Ac-ICVWQDWG(AIB)HRCT-NH2 | 12 | 1.50 |
| 16 | pharmacophore | Ac-ICVWQDWGAHRCT | 25 | 2.00 |
| 17 | pharmacophore | Ac-ICVVNDWGHHACT-NH2 | 11 | 60.00 |
| 18 | novel analogues | Ac-ICVYQDWGAHR(NMC)T-NH2 | 11 | 154.00 |
| 19 | structurekinetic | Ac-ICV(PAL)QDWGAHRCT-NH2 | 9 | 1.20 |
| 20 | pharmacophore | Ac-ICV(ALC)QDWGAHRCT | 27 | 53.60 |
| 21 | pharmacophore | Ac-ICVHQDWGHHRCT-NH2 | 21 | 10.50 |
| 22 | pharmacophore | Ac-ICVVQDWGAHACT-NH2 | 12 | 9.90 |
| 23 | structurekinetic | Ac-ICVWQDWGAHRCT-NH2 | 0 | 1.20 |
| 24 | pharmacophore | Ac-ICVWQD(OMW)GAHRCT-NH2 | 4 | 1000.00 |
| 25 | pharmacophore | Ac-ICLVQDWGHHRCT-NH2 | 8 | 10.00 |
| 26 | pharmacophore | Ac-ICVYQDWGAHRCT-NH2 | 23 | 3.80 |
| 27 | structurekinetic | Ac-ICVYQDWGAHRCT-NH2 | 4 | 2.40 |
| 28 | pharmacophore | Ac-ICVWQDWG(AIB)HRCT-NH2 | 29 | 1.50 |
| 29 | structurekinetic | Ac-ICVVQDWGHHRCT-NH2 | 15 | 4.50 |
| 30 | pharmacophore | Ac-ICVAQDWGAHRCI-NH2 | 7 | 12.00 |
| 31 | pharmacophore | Ac-ICLVNDWGHHRCT-NH2 | 9 | 8.30 |
| 32 | novel analogues | Ac-ICVYQD(NMW)GAHRCT-NH2 | 6 | 25.00 |
| 33 | pharmacophore | Ac-ICV(ALN)QDWGAHRCT | 31 | 1.80 |
| 34 | pharmacophore | Ac-ICVTQDWGHHRCT-NH2 | 19 | 68.30 |
| 35 | novel analogues | Ac-ICVYQ(NMD)WGAHRCT-NH2 | 5 | 44.00 |
| 36 | novel analogues | Ac-ICVYQDW(NMG)AHRCT-NH2 | 7 | 584.47 |
| 37 | novel analogues | Ac-ICVY(NMQ)DWGAHRCT-NH2 | 4 | 33.00 |
| 38 | novel analogues | Ac-ICVYQDWGAHRCT-NH2 | 0 | 2.40 |
| 39 | pharmacophore | Ac-LCVWQDWGRHQCF-NH2 | 14 | 131.00 |
| 40 | pharmacophore | Ac-ICVFQDWGHHRCT-NH2 | 22 | 10.20 |
| 41 | novel analogues | Ac-ICVYQDWGAH(NMR)CT-NH2 | 10 | 32.00 |
| 42 | novel analogues | Ac-ICVYQDWGA(NMH)RCT-NH2 | 9 | 94.00 |
| 43 | structurekinetic | Ac-ICV(OMW)QDWGPHRCT-NH2 | 14 | 0.54 |
| 44 | pharmacophore | Ac-DCVVQDWGHHRCT-NH2 | 18 | 22.00 |
| 45 | structurekinetic | Ac-ICV(OEY)QDWGAHRCT-NH2 | 6 | 1.30 |
| 46 | novel analogues | Ac-ICVYQDWG(NMA)HRCT-NH2 | 8 | 1000.00 |
| 47 | pharmacophore | CVVQDWGHHRC-NH2 | del1 | 33.00 |
| 48 | pharmacophore | CVVQDWGHC-NH2 | del9 | 600.00 |
| 49 | novel analogues | Ac–I(NMC)VYQDWGAHRCT-NH2 | 1 | 7.50 |
| 50 | novel analogues | Ac-ICV(NMY)QDWGAHRCT-NH2 | 3 | 1000.00 |
| 51 | pharmacophore | Ac-ICVVGDWGHHRCT-NH2 | 6 | 567.00 |
| 52 | pharmacophore | CVVQDWGHHRCT-NH2 | del0 | 25.00 |
| 53 | pharmacophore | ICVVQDWGHHRCT | 0 | 12.00 |
| 54 | pharmacophore | IAVVQDWGHHRAT | 5 (Linear) | 600.00 |
| 55 | pharmacophore | CVVQDWC-NH2 | del8 | 600.00 |
| 56 | pharmacophore | CAVQDWGHHRC | del10 | 1200.00 |
| 57 | pharmacophore | CWGHHRCT-NH2 | del4 | 600.00 |
| 58 | pharmacophore | CVVQDWAHHRC | del11 | 1200.00 |
| 59 | pharmacophore | CVQDWGHHRCT-NH2 | del7 | 600.00 |
| 60 | pharmacophore | CQDWGHHRCT-NH2 | del6 | 600.00 |
| 61 | pharmacophore | CDWGHHRCT-NH2 | del5 | 600.00 |
| 62 | pharmacophore | CHHRCT-NH2 | del2 | 600.00 |
| 63 | pharmacophore | CGHHRCT-NH2 | del3 | 600.00 |
a
The noncanonical amino acids studied are phosphotyrosine (PTR), O-methyltyrosine (OMY), N-methylthreonine (NMT), 5-methyltryptophan (MTR), 1-methyltryptophan (OMW), α-aminoisobutyric acid (AIB), N-methylcysteine (NMC), 1-pyrenylalanine (PAL), cyclohexylalanine (ALC), N-methyltryptophan (NMW), 1-naphthylalanine (ALN), N-methylaspartic acid (NMD), N-methylglycine (NMG), N-methylglutamine (NMQ), N-methyl-arginine (NMR), N-methylhistidine (NMH), O-ethyltyrosine (OMY), N-methylalanine (NMA), N-methyltyrosine (NMY). Several of these non-canonical amino acids were substituted in different positions on the Compstatin sequence. ACE and NH2 correspond to the N-terminal and C-terminal blocking groups acetyl and amide to keep the termini neutrally charged.