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Title: Real time detection of cell cycle regulator cyclin A on living tumor cells with europium emission
Authors: Li, H
Chadbourne, FL
Lan, R
Chan, CF
Chan, WL
Law, GL 
Lee, CS
Cobb, SL
Wong, KL
Issue Date: 2013
Publisher: Royal Society of Chemistry
Source: Dalton transactions : an international journal of inorganic chemistry, 2013, v. 42, no. 37, p. 13495-13501 How to cite?
Journal: Dalton transactions : an international journal of inorganic chemistry 
Abstract: Six water-soluble europium complexes (Eu-L1-Pn and Eu-L2-Pn, n = 1, 2 and 3) with one antenna chromophore, two different linkers (L1 and L2) and three proposed cyclin A specific peptides (P1: -GAKRRLIF-NH2; P 2: -GGAKRRLIF-NH2; P3: -Hex- GAKRRLIF-NH 2) have been synthesized. With structural information available, comparisons of the cyclin grooves of cyclin A and the six europium complexes have been made, and insights have been gained into the determinants for peptide binding and the foundation of differential binding. Experiment-wise, the linear and two-photon induced photophysical properties of these conjugates were monitored in aqueous solution. Numerous in situ/in vitro biological assays have been carried out, such as responsive emission changes in situ/in vitro, Western blot and cellular uptake. As imaging agents, complexes with peptides P 3: -Hex-GAKRRLIF-NH2 showed high selectivity to cyclin A in numerous cancer cells. When it comes to responsive optical signal changes, complex Eu-L2-P3 exhibited a threefold emission enhancement upon binding with cyclin A (100 nM cyclin A, φ = 8% to 21%, log KB = 5.83, detection limit = 5 nM), and this could be initiated by the shortened distance between the antenna and the lanthanide after they bind/get into cyclin A. It is promising that our compounds (especially compound Eu-L2-P3) could serve as the template for structure-guided efforts to develop potential imaging therapeutics on the basis of selective imaging of CDK2/cyclin A activity.
ISSN: 1477-9226
EISSN: 1477-9234
DOI: 10.1039/c3dt51053k
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