Peptide and Protein Tags for the Half-Life Extension of Therapeutic Agents: A Review Article Publisher Pubmed



Aboutalebi S ; Najafi F ; Yazdizadeh N ; Shafiee F
Source: Protein Journal Published:2026

Abstract

Although biological drugs have been considered as one of the effective and growing therapeutic approaches in the pharmaceutical industry in recent decades, the largest concern about them is the insufficient stability and rapid degradation in the bloodstream due to their structural nature. One of the effective methods for increasing the circulating half-life of peptide and protein drugs is the addition of half-life-extending tags, which prevent both the degradation of the biological drug and its glomerular filtration by various mechanisms, thereby increasing its half-life. This review focuses on peptide and protein tags used to enhance the pharmacokinetic profiles of biological drugs by increasing their half-life. It discusses various tags, including HSA (Human Serum Albumin), ABD (Albumin Binding Domain), DARPINS (Designed Ankyrin Repeat proteins), XTEN, CTP (Carboxy Terminal Peptide), ELP (Elastin Like Peptide), and others, and highlights both FDA-approved products and candidates currently in different stages of clinical development. In the meantime, special attention has been paid to albumin-binding domains and albumin-binding domain antibody (AlbudAb), which increases the half-life of biological drugs by binding to albumin, as the most abundant and stable protein in the body. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.