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设计炭疽热毒素的多效价抑制剂
Screening peptide libraries is a proven strategy for identifying inhibitors
of protein-ligand interactions. Compounds identified in these screens
often bind to their targets with low affinities. When the target protein
is present at a high density on the surface of cells or other biological
surfaces, it is sometimes possible to increase the biological activity
of a weakly binding ligand by presenting multiple copies of it on
the same molecule. We isolated a peptide from a phage display library
that binds weakly to the heptameric cell-binding subunit of anthrax
toxin and prevents the interaction between cell-binding and enzymatic
moieties. A molecule consisting of multiple copies of this nonnatural
peptide, covalently linked to a flexible backbone, prevented assembly
of the toxin complex in vitro and blocked toxin action in an animal
model. This result demonstrates that protein-protein interactions
can be inhibited by a synthetic, polymeric, polyvalent inhibitor in
vivo.
【引自Nat Biotechnol 2001 Oct;19(10):958-61】 |
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