Evidence that a second stereochemical centre in diacylglycerols defines interaction at the recognition site on protein kinase C

FEBS Letters

Garland, Lawrence G.¹  Beams, Richard M.²  Bonser, Robert W.¹  Thompson, Neil T.¹  Hodson, Harold F.² 

[1] Medicinal Chemistry, The Wellcome Research Laboratories, Langley Court, Beckenham BR3 3BS, England;Departments of Biochemical Sciences, The Wellcome Research Laboratories, Langley Court, Beckenham BR3 3BS, England

关键词: Protein kinase C;    Diacylglycerol;    Phorbol ester;    Structure/activity relationship;   

DOI  :  10.1016/0014-5793(88)80112-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The interaction of novel diacylglycerol analogues at the recognition site on protein kinase C has been evaluated using a modified [³H]phorbol dibutyrate binding assay and an established kinase activation assay. Studies with the 3-methyl analogues of 1,2-dihexanoyl-sn-glycerol have revealed a preferred stereochemical configuration at the C-3 position. Other chemical modifications have extended existing structure/activity relationships by showing that carbamates and sulphonyl esters cannot substitute for carboxylate esters and that cyclic acyl groups are active. Thus, most, if not all of the functionalities in the diacylglycerol molecule are required for interaction at the receptor on protein kinase C. Stereochemical specificity is required at C2 and C3.

【 授权许可】

Unknown