Table 1.
Salient Modifications of ptRNases that Enhance Cytotoxicity
| Ribonuclease | Tm (°C)a | Ribonucleolytic Activity (%)b | Ki or Kd (nM)c | IC50 (μM)d | Ze | Reference |
|---|---|---|---|---|---|---|
| Wild-type RNase A | 64 | 100 | 44 × 10−6 | >25 | +4 | Rutkoski et al. (2005) |
| G88R RNase A | 60 | 142 | 2.8 | 6.2 | +5 | Leland et al. (1998) |
| A4C/G88R/V188C RNase A | 69 | 94 | 0.65 | 3 | +5 | Klink and Raines (2000) |
| D38R/R39D/N67R/G88R RNase A | 56 | 75 | 1.4 × 103 | 0.19 | +6 | Rutkoski et al. (2005) |
| E49R/D53R/G88R RNase A | 54 | 5 | 2.6 | 1.9 | +9 | Fuchs et al. (2007) |
| E49R/D53R/G88R RNase A–R9 | 49 | 7 | 3.0 | 0.58 | +18 | Fuchs et al. (2007) |
| (RNase A)2 [SGRSGRSG linker] | 61 | 1.2 | ND | 12.9 | +10 | Leich et al. (2006) |
| (D38R/R39D/N67R/G88C RNase A)3 | ND | 17 | ND | 1.0 | +16 | Rutkoski et al. (2010) |
| Wild-type RNase 1 | 57 | 100 | 29 × 10−8 | >25 | +6 | Johnson et al. (2007b) |
| R39D/N67R/N88R/G89D/R91D RNase 1 | 53 | 81 | 28 | 5.69 | +3 | Johnson et al. (2007b) |
| PE5 (RNase 1–NLS) | 46 | ND | ND | 4.6 | +6 | Tubert et al. (2011) |
| Onconase® | 90 | 100 | ≥103 | 0.27 | +5 | Rutkoski et al. (2005) |
a
Values of Tm are the temperature at the midpoint of thermal denaturation, which can be monitored by ultraviolet or circular dichroism spectroscopy.
b
Values of ribonucleolytic activity are relative to the wild-type enzyme.
c
Values of the equilibrium dissociation constant (or inhibition constant) are for the complex with human RI.
d
Values of IC50 are for the incorporation of [methyl-3H]thymidine into the DNA of K-562 human leukemia cells.
e
Values of Z refer to the net molecular charge: Arg + Lys − Asp − Glu − Pyr (where “Pyr” refers to a pyroglutamate residue, which is found at the N-terminus of Onconase®).