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Issue 37, 2013
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Real time detection of cell cycle regulator cyclin A on living tumor cells with europium emission

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Abstract

Six water-soluble europium complexes (Eu–L11Pnnn and Eu–L22Pnnn, n = 1, 2 and 3) with one antenna chromophore, two different linkers (L11 and L22) and three proposed cyclin A specific peptides (P11: -GAKRRLIF-NH2; P22: -GGAKRRLIF-NH2; P33: -Hex- GAKRRLIF-NH2) 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 P33: -Hex-GAKRRLIF-NH2 showed high selectivity to cyclin A in numerous cancer cells. When it comes to responsive optical signal changes, complex Eu–L22P33 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–L22P33) 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.

Graphical abstract: Real time detection of cell cycle regulator cyclin A on living tumor cells with europium emission

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Publication details

The article was received on 22 Apr 2013, accepted on 08 Jul 2013 and first published on 08 Jul 2013


Article type: Paper
DOI: 10.1039/C3DT51053K
Citation: Dalton Trans., 2013,42, 13495-13501
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    Real time detection of cell cycle regulator cyclin A on living tumor cells with europium emission

    H. Li, F. L. Chadbourne, R. Lan, C. Chan, W. Chan, G. Law, C. Lee, S. L. Cobb and K. Wong, Dalton Trans., 2013, 42, 13495
    DOI: 10.1039/C3DT51053K

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