21.

On the top is the sequence of the native somatostatin peptide. The blue sequence in somatostatin represents a key pharmacophore in somatostatin, responsible for receptor binding. In somatostatin analogues, lysine (K) is conserved, while tryptophan is replaced with its stereoisomers in octreotide, lanreotide, vapreotide, and pasireotide. Phenylalanine is substituted with tyrosine, which has an additional hydroxyl group, and threonine is replaced with a more hydrophobic amino acid, such as valine, in lanreotide and vapreotide. Pasireotide incorporates the highest number of unnatural amino acids. In this analogue, cyclization occurs between the N- and C-terminal ends, while in octreotide, lanreotide, and vapreotide, cyclization involves the side chains of cysteine residues, similar to native somatostatin.