Stabilization of Therapeutic Proteins
Author(s)Chu, Jhih-Wei; Yin, Jin; Mazyar, Oleg; Goh, Lin-Tang; Yap, Miranda G.S.; Wang, Daniel I.C.; Trout, Bernhardt L.; ... Show more Show less
We present results of molecular simulations, quantum mechanical calculations, and experimental data aimed towards the rational design of solvent formulations. In particular, we have found that the rate limitation of oxidation of methionine groups is determined by the breaking of O-O bonds in hydrogen peroxide, not by the rate of acidic catalysis as previously thought. We have used this understanding to design molecular level parameters which are correlated to experimental data. Rate data has been determined both for G-CSF and for hPTH(1-34).
Molecular Engineering of Biological and Chemical Systems (MEBCS);
protein stabilization, excipients, molecular simulations, kinetics