Linear Peptide
A peptide with two free ends (N-terminus and C-terminus) and no ring-forming bonds. Linear peptides are simpler to synthesise but more susceptible to degradation. Many approved peptide drugs are linear, including semaglutide, liraglutide, leuprolide, and teriparatide, stabilised through chemical modifications.
Technical Context
Linear peptide stabilisation strategies: N-terminal modifications (acetylation blocks aminopeptidases, pyroglutamate forms naturally), C-terminal modifications (amidation blocks carboxypeptidases), internal modifications (D-amino acid substitution at protease-sensitive sites, N-methylation reducing protease recognition, Aib substitution for DPP-4 resistance), half-life extension (fatty acid conjugation for albumin binding — semaglutide, liraglutide; PEG conjugation — palopegteriparatide; Fc fusion — dulaglutide, romiplostim), and formulation-based approaches (depot formulations, implants). Linear peptide drug examples span diverse lengths: TRH (3 aa), leuprolide (9 aa), goserelin (10 aa), octreotide active sequence analogue alternatives (8-14 aa), semaglutide (31 aa), teriparatide (34 aa), and tesamorelin (44 aa). Each requires a tailored stability strategy based on its specific degradation profile.