Synthetic Approaches to Incorporation of Novel Amino Acids into Gonadotropin-Releasing Hormone Peptides

Publisher Summary This chapter presents the synthetic approaches to incorporation of novel amino acids into gonadotropin-releasing hormone (GnRH) peptides. When an endogenous peptide is selected as a therapeutic target and the in vitro potency has been optimized, then the in vivo activity is to be optimized. For this purpose, first, the peptide against enzymatic degradation needs to be stabilized to increase the metabolic stability. Second, the physicochemical properties have to be optimized to improve the pharmacokinetics in vivo . Third, a versatile and streamlined synthetic method is needed, which will allow to synthesize a large number of compounds, in a short period, to study the structure-activity relationships (SAR) of the target molecule. The chapter describes the execution of this strategy as applied to GnRH. Several agonists of GnRH are used for the treatment of prostate cancer, endometriosis, and other indications that are sex hormone dependent.