title: Symmetry requirements for effective blocking of pore-forming toxins: comparative study with alpha-, beta-, and gamma-cyclodextrin derivatives.
abstract: We compared the abilities of structurally related cationic cyclodextrins to inhibit Bacillus anthracis lethal toxin and Staphylococcus aureus α-hemolysin. We found that both β- and γ-cyclodextrin derivatives effectively inhibited anthrax toxin action by blocking the transmembrane oligomeric pores formed by the protective antigen (PA) subunit of the toxin, whereas α-cyclodextrins were ineffective. In contrast, α-hemolysin was selectively blocked only by β-cyclodextrin derivatives, demonstrating that both symmetry and size of the inhibitor and the pore are important.
authors.affiliation: Institute of Physical Chemistry, National Center for Scientific Research Demokritos, Aghia Paraskevi 15310, Athens, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Yannakopoulou
authors.forename: Laszlo
authors.initials: L
authors.lastname: Jicsinszky
authors.forename: Crysie
authors.initials: C
authors.lastname: Aggelidou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Mourtzis
authors.forename: Tanisha M
authors.initials: TM
authors.lastname: Robinson
authors.forename: Adiamseged
authors.initials: A
authors.lastname: Yohannes
authors.forename: Ekaterina M
authors.initials: EM
authors.lastname: Nestorovich
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Bezrukov
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Karginov
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry; D001427:Bacterial Toxins / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D006460:Hemolysin Proteins / Q000737:chemistry; D008968:Molecular Conformation; D013211:Staphylococcus aureus / Q000378:metabolism; D047391:alpha-Cyclodextrins / Q000737:chemistry*; D047392:beta-Cyclodextrins / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D047391:alpha-Cyclodextrins; C030325:anthrax toxin; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins