Functional characterization of peptide-based anthrax toxin inhibitors.
We have identified an optimized peptide inhibitor that can be used to develop potent anthrax toxin therapeutics. Anthrax toxin, an essential virulence factor of Bacillus anthracis, elicits many of the symptoms associated with the disease, and is responsible for death. The toxin is composed of a cell-binding component, protective antigen, and two enzymatic components, edema factor and lethal factor. The three proteins are secreted individually by the bacterium and then assemble into functional complexes on the surface of mammalian cells. These complexes are endocytosed, and the enzymatic components are translocated into the cytosol, where they exert their activities. We screened a phage display library for peptides that can bind the heptameric cell-binding subunit of anthrax toxin, and identified a novel peptide that can block toxin assembly. We made a series of mutant peptides and attached these peptides to polymer backbones to assess their inhibitory activities in vitro. This series of truncated peptide mutants was used to identify a minimal peptide sequence, TYWWLD, that can be used to develop potent polyvalent inhibitors of anthrax toxin.
Gujraty
Kunal
K
The Howard P. Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
Sadacharan
Skanda
S
Frost
Mia
M
Poon
Vincent
V
Kane
Ravi S
RS
Mogridge
Jeremy
J
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D020128:Inhibitory Concentration 50; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D019151:Peptide Library; D010455:Peptides; C030325:anthrax toxin