Table IV.
Biological Activity of V13K Analogs Against Different Gram-Negative (A) and Gram-Positive (B) Bacteria
| Antimicrobial Activity |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hemolytic Activity |
MICc (μg/ml) |
Therapeutic Index |
||||||||||
| Peptide Name |
Number of Positively Charged Residues |
Net Charge |
MHCa (μg/ml) |
Foldb |
P. aeruginosa PAOl |
E. coli C498 UB1005 |
E. coli C857 DH5α |
S. typhimurium C587 14208S |
GMg | Foldd | MHC/MICe | Foldf |
| A. Gram-negative bacteria | ||||||||||||
| +4S | 4 | +4 | 125.0 | 0.5 | >64 | 32 | 2 | >64 | 32.0 | 0.1 | 3.9 | 0.1 |
| V13K | 7 | +7 | 250.0 | 1.0 | 8 | 8 | 1 | 4 | 4.0 | 1.0 | 62.5 | 1.0 |
| +8 | 8 | +8 | 250.0 | 1.0 | 4 | 8 | 1 | 4 | 3.4 | 1.2 | 74.3 | 1.2 |
| +9 | 9 | +9 | <7.8 | 0.02 | 8 | 8 | 1 | 4 | 4.0 | 1.0 | 1.0 | 0.02 |
| +10 | 10 | +10 | <7.8 | 0.02 | 4 | 8 | 2 | 4 | 4.0 | 1.0 | 1.0 | 0.02 |
| Antimicrobial Activity |
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Hemolytic Activity |
MICc (μg/ml) |
Therapeutic Index |
|||||||||
| Peptide Name |
Number of Positively Charged Residues |
Net Charge |
MHCa (μg/ml) |
Foldb |
S. aureus C622 ATCC3923 |
S. epidermidis C621 |
B. subtilus C971 ATCC6633 |
GMg | Foldd | MHC/MICe | Foldf |
| B. Gram-positive bacteria | |||||||||||
| +4S | 4 | +4 | 125.0 | 0.5 | >64 | 64 | 32 | 80.6 | 0.5 | 1.6 | 0.3 |
| V13K | 7 | +7 | 250.0 | 1.0 | >64 | 16 | 32 | 40.3 | 1.0 | 6.2 | 1.0 |
| +8 | 8 | +8 | 250.0 | 1.0 | 32 | 8 | 32 | 20.2 | 2.0 | 12.4 | 2.0 |
| +9 | 9 | +9 | <7.8 | 0.02 | >64 | 8 | 32 | 32.0 | 1.3 | 0.1 | 0.02 |
| +10 | 10 | +10 | <7.8 | 0.02 | >64 | 8 | 16 | 25.4 | 1.6 | 0.2 | 0.02 |
MHC is the maximal peptide concentration that produces no hemolysis of human red blood cells after 18 h in the standard microtiter dilution method. When hemolytic activity was still observed at 7.8 μg/ml, a value of 3.9 μg/ml was used for calculation of the therapeutic index and fold improvement.
The fold improvement in hemolytic activity compared to that of lead compound, V13K.
MIC is minimal inhibitory concentration that inhibited growth of different strains in Mueller-Hinton (MH) medium at 37°C after 24 h. MIC is given based on four sets of determinations. When no detectable antimicrobial activity was observed at 64 μg/ml, a value of 128 μg/ml was used for calculation of the therapeutic index and fold improvement.
The fold improvement in antimicrobial activity (geometric mean data) compared to that of lead compound, V13K.
Therapeutic index is the ratio of the MHC value (μg/ml) over the geometric mean MIC value (μg/ml). Large values indicate greater antimicrobial specificity.
The fold improvement in therapeutic index compared to that of lead compound, V13K.
GM, geometric mean of the MIC values.