Design and synthesis of AX4697, a bisindolylmaleimide exo-affinity probe that labels protein kinase C alpha and beta.
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.
Liu
Yongsheng
Y
ActivX Biosciences, 11025 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Wu
Jiangyue
J
Weissig
Helge
H
Betancort
Juan M
JM
Gai
Wen Zhi
WZ
Leventhal
Phillip S
PS
Patricelli
Matthew P
MP
Samii
Babak
B
Szardenings
Anna K
AK
Shreder
Kevin R
KR
Kozarich
John W
JW
D020134:Catalytic Domain; D015195:Drug Design; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D013329:Structure-Activity Relationship
C533387:AX4697; D005456:Fluorescent Dyes; D007211:Indoles; D008301:Maleimides; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; C088060:bisindolylmaleimide