Table 2.
Sequence and activity of WCopW5 derivatives.
| Compound | Sequencea | Net charge | MW | Minimum inhibitory concentrations (μM)b | Hemolysis percent (%)c | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MDR P. aeruginosa | MDR A. baumannii | MDR S. aureus | MDR E. faecalis | 100 μM | 50 μM | 25 μM | ||||||||||||||||||
| Protegrin-1 | NH2 | R | G | G | R | L | C | Y | C | R | R | +7 | 2155.7 | 10 | 10 | 10 | 10 | 71.66 ±12.24 | 56.75 ±6.02 | 47.83 ±6.23 | ||||
| CONH2 | R | G | V | C | V | C | F | R | 1.25* | 1.25* | 5* | 1.25* | ||||||||||||
| Ptg C-ter 1 | NH2 | G | V | L | V | L | F | R | R | R | CONH2 | +4 | 1114.4 | >20 | >20 | >20 | >20 | 1.17 ±0.07 | 0.99 ±0.26 | 0.40 ±0.10 | ||||
| Ptg C-ter 2 | NH2 | G | V | L | V | W | F | R | R | R | CONH2 | +4 | 1187.5 | >20 | >20 | >20 | >20 | 1.80 ±0.07 | 1.14 ±0.02 | 0.52 ±0.05 | ||||
| Ptg C-ter 3 | NH2 | G | V | W | V | L | F | R | R | R | CONH2 | +4 | 1187.5 | >20 | >20 | >20 | >20 | 1.32 ±0.09 | 0.80 ±0.09 | 0.44 ±0.10 | ||||
| AcWL-1 | NH2 | W | L | L | L | L | L | R | R | R | CONH2 | +4 | 1237.6 | >20 | 2.5 | 10 | 10 | 36.35 ±3.00 | 20.52 ±1.25 | 11.89 ±1.24 | ||||
| AcWL-2 | NH2 | L | L | L | L | L | W | R | R | R | CONH2 | +4 | 1237.6 | >20 | >20 | 10 | 10 | 27.97 ±2.79 | 15.13 ± 2.05 | 14.39 ±0.70 | ||||
| AcWL-3 | NH2 | W | L | L | L | L | W | R | R | R | CONH2 | +4 | 1310.7 | >20 | 2.5 | 5 | 5 | 36.71 ±3.91 | 19.80 ±0.76 | 16.44 ±0.89 | ||||
| Hybrid-1 | NH2 | W | L | V | W | V | G | R | R | R | CONH2 | +4 | 1226.5 | >20 | >20 | >20 | >20 | 1.40 ±0.08 | 1.09 ±0.32 | 0.88 ±0.24 | ||||
| Hybrid-2 | NH2 | W | L | V | W | I | G | R | R | R | CONH2 | +4 | 1240.5 | >20 | 10 | >20 | >20 | 2.88 ±1.49 | 1.21 ±0.01 | 0.66 ±0.07 | ||||
| Hybrid-3 | NH2 | W | L | V | W | V | W | R | R | R | CONH2 | +4 | 1355.7 | >20 | 2.5 | 10 | 10 | 7.17 ±1.09 | 5.14 ±0.19 | 4.26 ±0.63 | ||||
| LWCopW29 (Hybrid-4) | NH2 | W | L | V | W | I | W | R | R | R | CONH2 | +4 | 1369.7 | >20 | 1.25 | 5 | 5 | 13.65 ±0.74 | 5.15 ±0.15 | 0.84 ±0.06 | ||||
| 10* | 0.31* | 1.25* | 1.25* | |||||||||||||||||||||
| WCopW29 | NH2 | w | l | v | w | i | w | r | r | r | CONH2 | +4 | 1369.7 | 5 | 0.63 | 1.25 | 1.25 | 12.00 ±1.27 | 5.40 ±0.56 | 0.43 ±0.01 | ||||
| 5* | 0.15* | 0.31* | 0.31* | |||||||||||||||||||||
| HLWCopW29-1 | NH2 | R | W | L | R | W | W | I | R | V | CONH2 | +4 | 1369.7 | 20 | 2.5 | 10 | 10 | 16.39 ±2.19 | 1.35 ±0.11 | 1.20 ±0.14 | ||||
| HLWCopW29-2 | NH2 | W | L | R | R | W | W | I | R | V | CONH2 | +4 | 1369.7 | >20 | 5 | 10 | 10 | 19.60 ±0.50 | 4.13 ±0.28 | 1.87 ±0.12 | ||||
| HLWCopW29-3 | NH2 | W | R | L | W | R | W | I | V | R | CONH2 | +4 | 1369.7 | >20 | 20 | 20 | 20 | 4.45 ±0.23 | 1.37 ±0.02 | 1.10 ±0.14 | ||||
| HLWCopW29-4 | NH2 | R | L | W | W | R | W | I | V | R | CONH2 | +4 | 1369.7 | >20 | 20 | 20 | 20 | 2.47 ±0.03 | 1.08 ±0.04 | 1.02 ±0.01 | ||||
aSequence of protegrin-1 and its C-terminal-truncated AcWL5 and WCopW5 derivatives. Lower case letters indicate d-form amino acids; capital letters, l-form. Hydrophilic position-preferring residues are remarked as bolded letters because of their critical role in matching the preferred membrane position profile.
bMICs in the high-salt CLSI standard condition. When considering the molecular weight of AMPs (≤1.52 kDa), a MIC of 2.5 μM (≤3.8 μg/ml) remarked as bold letters and a MIC of 1.25 μM (≤1.9 μg/ml) remarked as bold and underlined letters. The asterisk (*) indicates the MIC value measured in the presence of albumin (0.2%) and acetic acid (0.01%).
cHemolytic activity measured using 8% human red blood cells in PBS.