Synthesis, Binding Affinity, and Crosslinking of Monodentate Photoactive Phenothiazines to Calmodulin

Miroslaw Golinski, Paul J. DeLaLuz, Rey Floresca, David S. Watt, Tavner J. Delcamp, Thomas C. Vanaman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Various photoactive phenothiazines were synthesized that possessed a 2-azido, 3-azido, 2-benzoyl, or 1, 3, 4-trifluoro-2-azido functionality in combination with various modifications of the N-alkyl side chain. These phenothiazines were evaluated for their ability to inhibit the calmodulin-mediated activation of phosphodiesterase (PDE). All were active in inhibiting the action of calmodulin (CaM), but those possessing either a 3-azido and a 4-(4-methyl-1-piperazinyl)butyl side chain or a 2-benzoyl group and 3-(dimethylamino)propyl side chain proved to be most active (I50= 14 ± 3 μM and 7 ± 1 μM, respectively) when compared to the known inhibitor, chlorpromazine (CPZ, I50= 30 μM). Calmodulin was photolabeled with ca. 35% efficiency in a light- and calcium-dependent fashion using a radiolabeled analog, 3-azido-10-(4-(4-[14C]methyl-1-piperazinyl)butyl)phenothiazine, of one of these compounds. Competition studies using this radiolabeled analog and CPZ were consistent with binding to one or both of the hydrophobic binding pockets of CaM.

Original languageEnglish
Pages (from-to)549-557
Number of pages9
JournalBioconjugate Chemistry
Issue number5
StatePublished - 1995

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry


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