| 摘要 |
<p>Methods for inhibiting Factor XIII activity feature a ligand that forms at least one contact, at a distance of about 5 Å or less, with at least one amino acid residue of a Factor XIII monomer. Factor XIII inhibitors are selected or designed using the three-dimensional structure of Factor XIII as a guide. In one approach, inhibitory ligands are selected or designed based on the Factor XIII b-sandwich:core interface. In a second approach, inhibitors are selected or designed based on the catalytic site of Factor XIII. In a third approach, inhibitory ligands are selected or designed based on the Factor XIII dimer interface. In a fourth approach, inhibitory molecules were designed to occupy the Factor XIII binding site, and include an electrophilic moiety susceptible to nucleophilic displacement by the reactive Cys-314.</p> |
