title: 3D-QSAR analysis of conformationally constrained diacylglycerol (DAG) analogues as potent protein kinase C (PK-C) ligands.
abstract: A study of the quantitative structure activity relationships (QSARs) was performed based on the binding affinity (pKi) values of 32 protein kinase C (PK-C) ligands. The QSAR study was carried out by using both three-dimensional descriptors (the steric and electrostatic CoMFA fields) and the physicochemical properties (logP values). The CoMFA analysis provided a reasonable QSAR model, with a cross-validated q2 value of 0.671 and a conventional r2 value of 0.956, which was confirmed by the satisfactory prediction of the experimental binding affinity (pKi) values for a series of 3-alkylidene-5,5-disubstituted tetrahydro-2-furanones included in the test set. The resultant QSAR model will be useful for designing highly potent and selective PK-C ligands.
authors.affiliation: Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D004075:Diglycerides / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008968:Molecular Conformation; D011485:Protein Binding; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity
chemical_list: D004075:Diglycerides; D008024:Ligands; D011493:Protein Kinase C