title: Inhibiting bacterial toxins by channel blockage.
abstract: Emergent rational drug design techniques explore individual properties of target biomolecules, small and macromolecule drug candidates, and the physical forces governing their interactions. In this minireview, we focus on the single-molecule biophysical studies of channel-forming bacterial toxins that suggest new approaches for their inhibition. We discuss several examples of blockage of bacterial pore-forming and AB-type toxins by the tailor-made compounds. In the concluding remarks, the most effective rationally designed pore-blocking antitoxins are compared with the small-molecule inhibitors of ion-selective channels of neurophysiology.
authors.affiliation: Program in Physical Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Bezrukov
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC 20064, USA nestorovich@cua.edu.
authors.forename: Ekaterina M
authors.initials: EM
authors.lastname: Nestorovich
mesh_terms: D000992:Antitoxins / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000145:classification; D015195:Drug Design; D055808:Drug Discovery; D020128:Inhibitory Concentration 50; D018272:Porins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D018272:Porins
keywords: channel-blocking antitoxins; multivalent interactions; physical forces of efficient blockage; rational drug design; single molecule/protein interaction; structure-based drug discovery