Anticalins as alternative binding proteins for therapeutic use.
Members of the human lipocalin protein family exhibit four structurally hypervariable loops that form a ligand pocket, similar to the six complementarity-determining regions of antibodies. Using targeted random mutagenesis and selection, novel binding proteins, the so-called anticalins, have been engineered for the specific and tight complexation of low-molecular weight compounds as well as protein antigens, in particular medically relevant cell-surface targets. Based on recent in vitro and in vivo data, anticalins offer three mechanisms for application in human therapy: (i) as antagonists, for example, by binding to cellular receptors and blocking them from interaction with natural signaling molecules; (ii) as tissue-targeting vehicles, by localizing toxic molecules, cytokines or enzymes to disease-related cell-surface receptors; and (iii) as antidotes, by rapidly scavenging toxic or otherwise irritant compounds from the body. Compared with antibodies, anticalins provide several practical advantages because they are much smaller, consist of a single polypeptide chain, do not require disulfide bonds, and can easily be produced in microbial host cells.
Skerra
Arne
A
Lehrstuhl für Biologische Chemie, Technische Universität München, 85350 Freising-Weihenstephan, Germany. skerra@wzw.tum.de
D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D054834:Lipocalins / Q000737:chemistry / Q000276:immunology; D008958:Models, Molecular; D011485:Protein Binding; D015202:Protein Engineering; D017434:Protein Structure, Tertiary
D000906:Antibodies; D054834:Lipocalins