REVIEWS DDT • Volume 10, Number 1 • January 2005 Reviews • KEYNOTE REVIEW 23 www.drugdiscoverytoday.com Lipocalins are a widespread family of small, robust proteins that typically transport or store biological compounds which are either of low 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. The lipocalins represent a family of functionally diverse, small pro- teins that comprise 160–180 amino acid residues and have weak se- quence homology but high similarity at the tertiary structural level [1,2]. Members of this family have important biological functions in a variety of organisms, from bacteria to humans. The majority of lipocalins are responsible for the storage and transport of compounds that have low solubility or are chemically sensitive, such as vitamins, steroids and metabolic products [3]. The human plasma retinol-binding protein (RBP) was the first lipocalin for which a 3D structure was elucidated [4,5]; RBP transports the poorly soluble and oxidation-prone vitamin A from the liver, where it is stored as a fatty acid ester, to several target tissues. Some lipocalins appear to have a more specialized role in vertebrates [6], participating, for example, in olfaction and Steffen Schlehuber PIERIS Proteolab AG, Freising-Weihenstephan, Germany Arne Skerra* Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan, Germany *e-mail: skerra@wzw.tum.de 1359-6446/04/$ – see front matter ©2005 Elsevier Ltd. All rights reserved. PII: S1359-6446(04)03294-5 STEFFEN SCHLEHUBER Steffen Schlehuber was born in Fulda, Germany, and studied chemistry at the Technical University of Darmstadt, where he specialized in biochemistry. He went on to complete a doctoral thesis in the laboratory of Arne Skerra at the Technical University of Munich,Germany, obtaining his PhD in 2001. During his doctoral study,Schlehuber was involved in the development of anticalins, which are engineered ligand-binding proteins derived from natural lipocalin proteins. Steffen Schlehuber is cofounder and CSO of PIERIS Proteolab AG, a biotechnology company situated in Freising-Weihenstephan, Germany.Founded in 2001, PIERIS focuses on the development and commercialization of anticalins for therapeutic and diagnostic uses, predominantly in the area of oncology and cardiovascular diseases. ARNE SKERRA Arne Skerra was born in Wiesbaden, Germany, and studied chemistry at the Technical University of Darmstadt. In 1989, he received his PhD at the Ludwig-Maximilians University, Munich, where he had performed, under the supervision of Andres Plückthun and Ernst-Ludwig Winnacker, important research on the bacterial expression of functional antibody fragments. After spending one year as a postdoctoral research fellow with Greg Winter and Cesar Milstein at the MRC Laboratory of Molecular Biology in Cambridge, UK, he joined the department of Hartmut Michel at the Max-Planck-Institute of Biophysics in Frankfurt am Main. In 1994,Skerra became Professor of Protein Chemistry at the Technical University of Darmstadt.Four years later he moved to the Technical University of Munich, where he was appointed a Full Professor to the Chair of Biological Chemistry at the Life Science Campus,Weihenstephan. Skerra is Chairman of the study group on protein engineer- ing and design at the Society for Biochemistry and Molecular Biology and a Board Member of the biochemistry section of the Society of German Chemists. In 2001,he cofounded the biotechnology start-up company PIERIS Proteolab AG. Lipocalins are promising drug candidates, either based on their natural ligand-binding functions or as engineered ‘anticalins’ with novel specificities. Keynote review: Lipocalins in drug discovery: from natural ligand-binding proteins to ‘anticalins’ Steffen Schlehuber and Arne Skerra