Designing a polyvalent inhibitor of anthrax toxin.
Nat Biotechnol
; 19(10): 958-61, 2001 Oct.
Article
in En
| MEDLINE
| ID: mdl-11581662
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Bacterial Toxins
/
Antigens, Bacterial
Limits:
Animals
Language:
En
Journal:
Nat Biotechnol
Journal subject:
BIOTECNOLOGIA
Year:
2001
Document type:
Article
Affiliation country: