Lipocalins in drug discovery: From natural ligand-binding proteins to ‘anticalins’

• Published in: Drug Discovery Today Vol. 10; no. 1; pp. 23 - 33
• Main Authors: Schlehuber, Steffen, Skerra, Arne
• Format: Book Review Journal Article
• Language: English
• Published: England Elsevier Ltd 2005
• Subjects: Animals; Antidotes - therapeutic use; Bilin-binding protein; Calycin; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Carrier Proteins - physiology; Drug Design; Hapten; Humans; Ligands; Plasma protein; Protein Binding; Protein engineering; Retinol-binding protein; Retinol-Binding Proteins - metabolism; Retinol-Binding Proteins - physiology; Retinol-Binding Proteins, Plasma; Technology, Pharmaceutical - methods; Technology, Pharmaceutical - trends; Protein engineering; Pharmaceutical Science; Chemical Biology; Biochemistry; Bilin-binding protein; Plasma protein; Drug Discovery; Hapten; Calycin; Retinol-binding protein
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/S1359-6446(04)03294-5

Lipocalins, an abundant family of ligand-binding and -transport proteins, have attracted attention as potential drugs, either based on their natural binding function or with engineered ligand specificities, as so-called ‘anticalins’ Lipocalins are a widespread family of small, robust proteins that typically transport or store biological compounds which are either oflow solubility or are chemically sensitive, including vitamins, steroid hormones, odorants and various secondary metabolites. There are approximately ten different lipocalins in the human body, with the plasma retinol-binding protein being the most well known. Some lipocalins have a pathophysiological role, which opens possibilities for their use in medical applications. Furthermore, lipocalins from blood-sucking insects have evolved as scavengers for mediators of inflammation. As well as using the natural ligand-binding function, lipocalins have also been recruited as scaffolds for the design of artificial binding proteins termed ‘anticalins’®. These novel proteins have potential applications as antidotes, antagonistic protein therapeutics or as target-recognition modules in a new generation of immunotoxins.