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Symmetry Complementarity‐Guided Design of Anthrax Toxin Inhibitors Based on β‐Cyclodextrin: Synthesis and Relative Activities of Face‐Selective Functionalized Polycationic Clusters
Author(s) -
DíazMoscoso Alejandro,
MéndezArdoy Alejandro,
OrtegaCaballero Fernando,
Benito Juan M.,
Ortiz Mellet Carmen,
Defaye Jacques,
Robinson Tanisha M.,
Yohannes Adiamseged,
Karginov Vladimir A.,
García Fernández José M.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000419
Subject(s) - chemistry , anthrax toxin , combinatorial chemistry , amine gas treating , cyclodextrin , cationic polymerization , bacillus anthracis , alkyne , toxin , stereochemistry , catalysis , polymer chemistry , biochemistry , organic chemistry , biology , fusion protein , bacteria , genetics , gene , recombinant dna
Three new series of potential anthrax toxin inhibitors based on the β‐cyclodextrin (βCD) scaffold were developed by exploiting face‐selective Cu I ‐catalyzed azide–alkyne 1,3‐cycloadditions, amine–isothiocyanate coupling, and allyl group hydroboration–oxidation/hydroxy → amine replacement reactions. The molecular design follows the “symmetry–complementarity” concept between homogeneously functionalized polycationic βCD derivatives and protective antigen (PA), a component of anthrax toxin known to form C 7 ‐symmetric pores on the cell membrane used by lethal and edema factors to gain access to the cytosol. The synthesis and antitoxin activity of a collection of βCD derivatives differing in the number, arrangement, and face location of the cationic elements are reported herein. These results set the basis for a structure–activity relationship development program of new candidates to combat the anthrax threat.