title: Bridged peptide macrocycles as ligands for PDZ domain proteins.
abstract: [reaction: see text] Conformationally constrained side chain-bridged cyclic peptides were prepared using bis-carboxylic acid ring spacers. These macrocyles were designed to inhibit protein-protein interactions mediated by the third PDZ domain (PDZ3) of a mammalian neuronal protein, PSD-95. Isothermal titration calorimetry (ITC) experiments measured dissociation constants in the low micromolar range. For each compound, the change in entropy (TdeltaS) of binding either is comparable in magnitude to the enthalpy change (deltaH) or is the predominant driving force for association.
authors.affiliation: Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA.
authors.forename: Gomika
authors.initials: G
authors.lastname: Udugamasooriya
authors.forename: Dorina
authors.initials: D
authors.lastname: Saro
authors.forename: Mark R
authors.initials: MR
authors.lastname: Spaller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D013816:Thermodynamics
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D051528:Guanylate Kinases