2-Benzyl and 2-phenyl-3-hydroxypropyl pivalates as protein kinase C ligands.
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.
Lee
Jeewoo
J
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. jeewoo@snu.ac.kr
Lee
Ju-Hyun
JH
Kim
Su Yeon
SY
Perry
Nicholas A
NA
Lewin
Nancy E
NE
Ayres
Jolene A
JA
Blumberg
Peter M
PM
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
D008024:Ligands; D010421:Pentanoic Acids; D010704:Phorbols; C005566:pivalic acid; D051571:Protein Kinase C-alpha