Amplification of bifunctional ligands for calmodulin from a dynamic combinatorial library.
A well known strategy to prepare high affinity ligands for a biological receptor is to link together low affinity ligands. DCC (dynamic combinatorial chemistry) was used to select bifunctional protein ligands with high affinity relative to the corresponding monofunctional ligands. Thiol to disulfide linkage generated a small dynamic library of bifunctional ligands in the presence of calmodulin, a protein with two independently mobile domains. The binding constant of the bifunctional ligand (disulfide) most amplified by the presence of calmodulin is nearly two orders of magnitude higher than that of the corresponding monofunctional ligand (thiol).
Milanesi
Lilia
L
Centre for Chemical Biology, Krebs Institute for Biomolecular Science, Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK.
Hunter
Christopher A
CA
Sedelnikova
Svetlana E
SE
Waltho
Jonathan P
JP
D002147:Calmodulin / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D004220:Disulfides / Q000737:chemistry*; D008024:Ligands
D002147:Calmodulin; D004220:Disulfides; D008024:Ligands