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Amplification of Bifunctional Ligands for Calmodulin from a Dynamic Combinatorial Library
Author(s) -
Milanesi Lilia,
Hunter Christopher A.,
Sedelnikova Svetlana E.,
Waltho Jonathan P.
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200500357
Subject(s) - bifunctional , ligand (biochemistry) , calmodulin , chemistry , combinatorial chemistry , thiol , stereochemistry , biochemistry , receptor , enzyme , catalysis
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).