title: Synthesis of potent inhibitors of anthrax toxin based on poly-L-glutamic acid.
abstract: We report the synthesis of biodegradable polyvalent inhibitors of anthrax toxin based on poly-L-glutamic acid (PLGA). These biocompatible polyvalent inhibitors are at least 4 orders of magnitude more potent than the corresponding monovalent peptides in vitro and are comparable in potency to polyacrylamide-based inhibitors of anthrax toxin assembly. We have elucidated the influence of peptide density on inhibitory potency and demonstrated that these inhibitory potencies are limited by kinetics, with even higher activities seen when the inhibitors are preincubated with the heptameric receptor-binding subunit of anthrax toxin prior to exposure to cells. These polyvalent inhibitors are also effective at neutralizing anthrax toxin in vivo and represent attractive leads for designing biocompatible anthrax therapeutics.
authors.affiliation: The Howard P. Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Joshi
authors.forename: Arundhati
authors.initials: A
authors.lastname: Saraph
authors.forename: Vincent
authors.initials: V
authors.lastname: Poon
authors.forename: Jeremy
authors.initials: J
authors.lastname: Mogridge
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kane
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002460:Cell Line; D018698:Glutamic Acid / Q000737:chemistry* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D010455:Peptides; D011108:Polymers; C030325:anthrax toxin; D018698:Glutamic Acid