| he peptide, thymopentin, has recently been used clinically in the treatment of auto immune diseases, rheumatoid arthritis and as an adjuvant in vaccinations. The proposed stability studies of thymopentin are challenged with two main goals. The first is to develop a faster, more cost effective non-isothermal method that could be used in lieu of isothermal methods. The second goal is to enhance the stability of thymopentin by manipulating the peptide environment or its primary structure. Hopefully, the results of this study can be used to better understand the chemical and biological stability of peptide formulations in general. A greater stability is desired because thymopentin has an extremely short half-life (only 30 seconds) in human plasma, which is due to enzymatic degradation. The proposed stability study was quantified by isothermal and non-isothermal methods. A comparison of the kinetic parameters obtained by these two methods was also performed. The traditional isothermal method of achieving stability is undesirable due to the high cost and limited supply of peptide pharmaceuticals. Therefore, the development of a faster, more cost-effective test for stability would greatly aid experimentation. A non-isothermal method would use less of the product and take months off of time required to run trials.;The proposed studies investigated the influence of pH, temperature, ionic strength, and buffer species on the rate of degradation of model peptides. Four approaches were designed to attempt to prolong thymopentin stability and its circulating time in vivo. The first approach was to create pro-drugs by substituting asparagine for aspartic acid in the thymopentin amino acid sequence so as to increase the circulating time of thymopentin. It is hoped that the pro-drug will revert to thymopentin by a deamidation reaction. The second approach substituted tryptophan for tyrosine of thymopentin, and then increased its stability by using... |
