Synthesis of Red-Shifted 8-Hydroxyquinoline Derivatives Using Click Chemistry and Their Incorporation into Phosphorylation Chemosensors

• Published in: Journal of organic chemistry 2009-10, Vol.74 (19), p.7309-7314
• Main Authors: González-Vera, Juan A, Luković, Elvedin, Imperiali, Barbara
• Format: Article
• Language: English
• Subjects: Analytical chemistry; Chemistry; Exact sciences and technology; Fluorescent Dyes - chemistry; General, instrumentation; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Molecular Structure; Organic chemistry; Oxyquinoline - chemical synthesis; Oxyquinoline - chemistry; Peptides; Phosphorylation; Preparations and properties; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo901369k

Protein phosphorylation is a ubiquitous post-translational modification, and protein kinases, the enzymes that catalyze the phosphoryl transfer, are involved in nearly every aspect of normal, as well as aberrant, cell function. Here we describe the synthesis of novel, red-shifted 8-hydroxyquinoline-based fluorophores and their incorporation into peptidyl kinase activity reporters. Replacement of the sulfonamide group of the sulfonamido-oxine (1, Sox) chromophore, which has been previously used in kinase sensing, by a 1,4-substituted triazole moiety prepared via click chemistry resulted in a significant bathochromic shift in the fluorescence excitation (15 nm) and emission (40 nm) maxima for the Mg2+ chelate. Furthermore, when a click derivative was incorporated into a chemosensor for MK2, the kinase accepted the new substrate as efficiently as the previously reported Sox-based sensor. Taken together, these results extend the utility range of kinase sensors that are based on chelation-enhanced fluorescence (CHEF).