Table 2.
Thermodynamic stabilities of insulin analogs
| Analog | ΔGu* (kcal mol−1) | Cmid (M) | m† (kcal mol−1 M−1) |
| Human insulin | 3.2 ± 0.1‡ | 5.2 ± 0.1 | 0.62 ± 0.02 |
| OrnB29 -insulin | 3.2 ± 0.1 | 5.0 ± 0.1 | 0.64 ± 0.01 |
| TyrB24, OrnB29-insulin | 2.3 ± 0.1 | 4.7 ± 0.2 | 0.49 ± 0.03 |
| Bovine insulin§ | 3.3 ± 0.1 | 4.6 ± 0.1 | 0.72 ± 0.02 |
| Insulin lispro¶ | 2.9 ± 0.1 | 4.9 ± 0.2 | 0.59 ± 0.01 |
| TyrB24-insulin lispro | 2.3 ± 0.1 | 4.9 ± 0.2 | 0.47 ± 0.02 |
Parameters were inferred from CD-detected guanidine denaturation data by application of a two-state model; uncertainties represent fitting errors for a given dataset.
The m-value [slope Δ(G)/Δ(M)] correlates with extent of hydrophobic surfaces exposed on denaturation.
Estimates of ΔGu pertain to insulin in 50 mM KCl and 10 mM KPi (pH 7.4) at 25 °C.
Bovine insulin differs from human insulin at three sites (ThrB30→Ala, ThrA8→Ala and IleA10→Val), representative of natural variation among species; further variation is provided by porcupine insulin (SI Appendix, Fig. S14 and Table S9).
Insulin lispo (the active component of Humalog; Lilly) contains paired substitutions ProB28→Lys (K) and LysB29→Pro (P); the analog is thus designated KP-insulin.