Linear Peptide

Linear peptides are unbranched amino acid chains held together by peptide bonds, with an unmodified N-terminus at one end, an unmodified C-terminus at the other, and no covalent bond closing them into a ring. Most research peptides belong here — including BPC-157, ipamorelin, GHRH analogs and most incretin mimetics.

Advantages and drawbacks of a linear chain

The benefits are practical ones. Solid-phase synthesis produces linear sequences directly, without an extra cyclisation step, which means better yields and a lower price per milligram; analysis is also easier, since mass and retention time between them mostly confirm identity without any questions about connectivity.

The downside is vulnerability. Open ends are attacked by aminopeptidases and carboxypeptidases, and a flexible chain explores many shapes, so its intrinsic affinity is frequently below that of a constrained counterpart. For that reason linear peptides are more often where modification begins than where it ends: acetylating the N-terminus and amidating the C-terminus block the ends, while DAC or PEGylation delay elimination. Compare our entry on cyclic peptides, and the explainer on sequence notation.

Related terms

native sequence · analog