title: 2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands.
abstract: A series of 2-benzyl and 2-phenyl-3-hydroxypropyl pivalates designed to incorporate the principal pharmacophores of phorbol esters have been synthesized and tested as PKC-alpha ligands. Among the analogues, 13c exhibited the most potent binding affinity with a Ki = 0.7 microM. The synthesized analogues were subjected to molecular modeling analysis based on two alternative models of the phorbol pharmacophore and a docking study of 13c was carried out.
authors.affiliation: Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. jeewoo@snu.ac.kr
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Perry
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Lewin
authors.forename: Jolene A
authors.initials: JA
authors.lastname: Ayres
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
mesh_terms: D001665:Binding Sites; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010421:Pentanoic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010704:Phorbols / Q000737:chemistry / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010421:Pentanoic Acids; D010704:Phorbols; C005566:pivalic acid; D051571:Protein Kinase C-alpha