Abstract:
Controlling certain diseases using peptide drugs has remarkably increased in the past
two decades. In this regard, a generic formulation is an upfront solution to fulfill market demands. Ganirelix, a leading peptide active pharmaceutical ingredient (API) primarily used as a gonadotropin-releasing hormone antagonist (GnRH), has established
a potential market value worldwide. But its generic formulation mandates detailed
impurity profiles from a synthetic source and contemplates the sameness of a
reference-listed drug (RLD). Post-chemical synthesis and processing of Ganirelix,
some commercial sources have revealed two new potential impurities among many
known, which show the deletion of an ethyl group from the hArg(Et)2 residue at the
sixth and eighth positions, named des-ethyl-Ganirelix. These impurities are unprecedented in traditional peptide chemistry, and such monoethylated-hArg building
blocks are not easily accessible commercially to synthesize these two impurities.
Here, we have outlined the synthesis, purification, and enantiomeric purity characterization of the amino acids and their incorporation in the Ganirelix peptide sequence
to synthesize these potential peptide impurities. This methodology will enable the
convenient synthesis of side-chain substituted Arg and hArg derivatives in peptide
drug discovery platforms.
