Dynamic combinatorial carbohydrate libraries: probing the binding site of the concanavalin A lectin.
Dynamic combinatorial chemistry (DCC) has emerged as an efficient approach to receptor/ligand identification based on the generation of combinatorial libraries by reversible interconversion of the library constituents. In this study, the implementation of such libraries on carbohydrate-lectin interactions was examined with the plant lectin Concanavalin A as a target species. Dynamic carbohydrate libraries were generated from a pool of carbohydrate aldehydes and hydrazide linker/scaffold components through reversible acylhydrazone exchange, resulting in libraries containing up to 474 constituents. Dynamic deconvolution allowed the efficient identification of the structural features required for binding to Concanavalin A and the selection of a strong binder, a tritopic mannoside, showing an IC(50)-value of 22 microM.
Ramström
Olof
O
Laboratoire de Chimie Supramoléculaire, ISIS-Université Louis Pasteur, 8, allée Gaspard Monge, BP 70028, 67083 Strasbourg Cedex, France.
Lohmann
Sophie
S
Bunyapaiboonsri
Taridaporn
T
Lehn
Jean-Marie
JM
D001665:Binding Sites; D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003208:Concanavalin A / Q000737:chemistry*; D037102:Lectins / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D010944:Plants / Q000737:chemistry
D002241:Carbohydrates; D037102:Lectins; D008024:Ligands; D003208:Concanavalin A