Peptide chemists have a myriad of approaches available to optimize lead peptide structures for activity, potency and the desired selectivity for the target of interest. Thus multiple modifications and/or longer-range structural features (e.g. cyclization) are often necessary to obtain the desired stability. For example, while gonadotropin releasing hormone (GnRH) already contains pyroglutamic acid at the N-terminus and a C-terminal amide, clinically used analogs contain a D-amino acid at position 6 in the middle of the peptide to stabilize the peptides to metabolism as well as modified C-termini.
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