Fc Fusion Peptide

An Fc fusion joins a peptide or protein to the crystallisable fragment of an immunoglobulin G. Expressed in mammalian cells from a single gene, it is a dimer because Fc chains pair through hinge disulfides, so it carries two copies of the peptide. Two things extend its life: at roughly 60 kilodaltons it is far above the kidney's filtration threshold, and the Fc binds the neonatal Fc receptor, which recycles it into the blood as it does antibodies.

Dulaglutide is the example. Two copies of a GLP-1 analogue, with glycine at position 8 to block DPP-4, are joined by a glycine-serine linker to a human IgG4 Fc mutated to weaken Fc-gamma receptor and complement binding; the molecule has a half-life of roughly five days and was approved in 2014 through a biologics licence rather than a drug application. Romiplostim hangs four copies of a thrombopoietin-mimetic peptide on an IgG1 Fc.

Fc fusion gives the longest exposure of the half-life extensions and needs no chemistry after expression, but the product is a glycoprotein, with cell-line-dependent glycans, anti-drug antibody risk at the junction and antibody-style manufacturing. The peptide also has to work while attached to a 50-kilodalton tail, which costs potency at some receptors and, where clustering helps, adds it.

A sequence block can show the active peptide segment, but the linker and the roughly 230-residue Fc are protein; the molecule cannot be written as a residue string or made by solid-phase synthesis. It falls on the biologic side of the 40-amino-acid boundary, so there is no generic of dulaglutide, only a biosimilar pathway, and a listing offering it as a synthetic peptide can at best be the bare 31-residue GLP-1 segment, which without its Fc lasts minutes.