| abstract |
Disclosed are oligonucleotides and methods for inhibiting selectins. The oligonucleotides of the invention specifically bind L-selectin and can be isolated by systematic evolution of ligands by exponential enrichment (SELEX) technology. Preferably, the method involves non-covalently binding the selectin receptor globulin to protein A sepharose beads. The oligonucleotides are useful for blocking selectin-dependent interactions with natural ligands in vivo and for diagnostic tests in vitro-cell surface and soluble selections. Clinically, the oligonucleotides can be administered to patients in methods for treating a variety of inflammatory and postischemic pathologies, such as ischemia-reperfusion injury, acute inflammatory states, and chronic immune responses. A specific modification of the previously described modifications are: (a) carrying out binding at anion concentrations < 160mM, i.e., close to physiological; (b) eluting by chelating Ca++, thereby obtaining oligos binding the Ca++ dependent lectin domain; (c) using low 1-5 mM EDTA for elution, avoiding non-specific elution; (d) doing selection at 22-37 °C to avoid loss of ligand structure if initial selection is done at 4 °C. |