Amplification of Bifunctional Ligands forCalmodulin from a Dynamic Combinatorial Library

Abstract

[eng] A well known strategy to prepare high affinity ligands for a biological re-ceptor is to link together low affinity ligands. DCC (dynamic combinatorialchemistry) was used to select bifunctional protein ligands with high affinity relativeto the corresponding monofunctional ligands. Thiol to disulfide linkage generateda small dynamic library of bifunctional ligands in the presence of calmodulin, aprotein with two independently mobile domains. The binding constant of the bi-functional ligand (disulfide) most amplified by the presence of calmodulin isnearly two orders of magnitude higher than that of the corresponding monofunc-tional ligand (thiol).