Enhanced apoptotic activity of a structurally optimized form of galectin-1.
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.
Bättig
Patrick
P
Cytos Biotechnology AG, Wagistrasse 25, 8952 Schlieren-Zürich, Switzerland.
Saudan
Philippe
P
Gunde
Tea
T
Bachmann
Martin F
MF
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D019281:Dimerization; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006386:Hemagglutination Tests; D051379:Mice; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D037483:Galectin 1