Thermodynamic profiling of conformationally constrained cyclic ligands for the PDZ domain.
Inspired by structure-based design and tailored for combinatorial preparation, a series of novel cyclic peptides has been developed to yield binding ligands for the third PDZ domain (PDZ3) of PSD-95. These side chain-side chain bridged peptides permit the systematic expansion or contraction of ring size, which is intended to maximize the conformational diversity of the ensemble. Isothermal titration calorimetry (ITC) was used to measure the dissociation constants (K(d)) and associated thermodynamic binding parameters.
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Tao
T
Li
Dorina
D
Saro
Mark R
MR
Spaller
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites / Q000502:physiology; D015815:Cell Adhesion Molecules; D008024:Ligands; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D013816:Thermodynamics
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D008024:Ligands; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C423943:PDZD2 protein, human; C033652:postsynaptic density proteins