Enhanced apoptotic activity of a structurally optimized form of galectin-1.

Journal article

Galectin-1 is a homodimeric protein with potent anti-inflammatory properties due to its ability to induce apoptosis in thymocytes and T cells. The galectin-1 subunits are not covalently linked but the monomers are in a dynamic equilibrium with the dimeric form. Since the affinity of the monomers for each other is rather low (in the range of 10(-5)M), the in vivo efficacy of galectin-1 is limited because the equilibrium is shifted towards the inactive monomeric form at lower concentrations. In order to overcome this problem, we designed a covalently linked form of the dimer based on the galectin-1 crystal structure. Here we show that this irreversibly dimeric form of galectin-1 is a potent inducer of apoptosis in murine thymocytes as well as murine mature T cells at concentrations 10-fold lower than wild-type galectin-1. This structurally optimized form of galectin-1 may therefore be a potentially powerful tool to treat chronic inflammatory diseases.

Authors: Bättig, P; Saudan, P; Gunde, T; Bachmann, M

• Publication status: Published
• Journal: Molecular immunology
• Volume: 41
• Issue: 1
• Pages: 9-18
• Publication date: 2004-05-01
• DOI: 10.1016/j.molimm.2004.02.004
• EISSN: 1872-9142
• ISSN: 0161-5890
• Language: English
• Keywords: T-Lymphocytes; Spleen; Cells, Cultured; Galectin 1; Animals; Thymus Gland; Mice; Dimerization; Hemagglutination Tests; Amino Acid Sequence; Molecular Sequence Data; Apoptosis