Polyvalency: a promising strategy for drug design.
The simultaneous binding of multiple ligands on one entity to multiple receptors on another can result in an affinity that is significantly greater than that for the binding of a single ligand to a single receptor. This concept of "polyvalency" can be used to design molecules that are potent inhibitors of toxins and pathogens. We describe the design of potent polyvalent inhibitors that neutralize anthrax toxin in vivo as well as our attempts to elucidate the relationship between inhibitor structure and activity. We also highlight promising future avenues for research in polyvalent drug design.
Vance
David
D
The Howard P. Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110, 8th Street, Ricketts Building, Troy, New York 12180, USA.
Shah
Mrinal
M
Joshi
Amit
A
Kane
Ravi S
RS
D000942:Antigens, Bacterial / Q000737:chemistry; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D011956:Receptors, Cell Surface; C030325:anthrax toxin