Design and synthesis of AX4697, a bisindolylmaleimide exo-affinity probe that labels protein kinase C alpha and beta

Yongsheng Liu; Jiangyue Wu; Helge Weissig; Juan M Betancort; Wen Zhi Gai; Phillip S Leventhal; Matthew P Patricelli; Babak Samii; Anna K Szardenings; Kevin R Shreder; John W Kozarich

doi:10.1016/j.bmcl.2008.08.045

Design and synthesis of AX4697, a bisindolylmaleimide exo-affinity probe that labels protein kinase C alpha and beta

Bioorg Med Chem Lett. 2008 Nov 15;18(22):5955-8. doi: 10.1016/j.bmcl.2008.08.045. Epub 2008 Aug 19.

Authors

Yongsheng Liu¹, Jiangyue Wu, Helge Weissig, Juan M Betancort, Wen Zhi Gai, Phillip S Leventhal, Matthew P Patricelli, Babak Samii, Anna K Szardenings, Kevin R Shreder, John W Kozarich

Affiliation

¹ ActivX Biosciences, 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA.

PMID: 18774710
DOI: 10.1016/j.bmcl.2008.08.045

Abstract

The synthesis and biochemical characterization of AX4697, a fluorescent, bisindolylmaleimide-derived probe for PKCalpha and beta, is described. AX4697 was able to quantify changes in PKC expression in drug-treated Jurkat cells and was shown to covalently label PKCalpha on C619, a residue that sits just outside the active site.

MeSH terms

Catalytic Domain
Drug Design
Fluorescent Dyes / chemical synthesis*
Fluorescent Dyes / chemistry
Fluorescent Dyes / pharmacology*
Humans
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology*
Jurkat Cells
Maleimides / chemical synthesis*
Maleimides / chemistry
Maleimides / pharmacology*
Molecular Structure
Protein Kinase C / metabolism*
Protein Kinase C beta
Protein Kinase C-alpha / metabolism*
Structure-Activity Relationship

Substances

AX4697
Fluorescent Dyes
Indoles
Maleimides
Protein Kinase C
Protein Kinase C beta
Protein Kinase C-alpha
bisindolylmaleimide