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

Hongguang Li; Frances L. Chadbourne; Rongfeng Lan; Chi-Fai Chan; Wai-Lun Chan; Ga-Lai Law; Chi-Sing Lee; Steven L. Cobb; Ka-Leung Wong

doi:10.1039/c3dt51053k

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

Hongguang Li, Frances L. Chadbourne, Rongfeng Lan, Chi-Fai Chan, Wai-Lun Chan, Ga-Lai Law, Chi-Sing Lee, Steven L. Cobb, Ka-Leung Wong

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

10 Citations (Scopus)

Abstract

Six water-soluble europium complexes (Eu-L₁-P_n and Eu-L₂-P_n, 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 K_B = 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. © 2013 The Royal Society of Chemistry.

Original language	English
Pages (from-to)	13495-13501
Journal	Dalton Transactions
Volume	42
Issue number	37
DOIs	https://doi.org/10.1039/c3dt51053k
Publication status	Published - 7 Oct 2013
Externally published	Yes

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Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

Funding

The work described in this paper was partially supported by grants from the Research Grants Council of the Hong Kong SAR (HKBU 203012) and a grant from the HKBU (FRG2/11-12/003).

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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@article{09d0aa0f224c436fb35a0b1543e6dd7d,

title = "Real time detection of cell cycle regulator cyclin A on living tumor cells with europium emission",

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. {\textcopyright} 2013 The Royal Society of Chemistry.",

author = "Hongguang Li and Chadbourne, {Frances L.} and Rongfeng Lan and Chi-Fai Chan and Wai-Lun Chan and Ga-Lai Law and Chi-Sing Lee and Cobb, {Steven L.} and Ka-Leung Wong",

note = "Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].",

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T1 - Real time detection of cell cycle regulator cyclin A on living tumor cells with europium emission

AU - Li, Hongguang

AU - Chadbourne, Frances L.

AU - Lan, Rongfeng

AU - Chan, Chi-Fai

AU - Chan, Wai-Lun

AU - Law, Ga-Lai

AU - Lee, Chi-Sing

AU - Cobb, Steven L.

AU - Wong, Ka-Leung

N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

PY - 2013/10/7

Y1 - 2013/10/7

N2 - 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. © 2013 The Royal Society of Chemistry.

AB - 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. © 2013 The Royal Society of Chemistry.

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U2 - 10.1039/c3dt51053k

DO - 10.1039/c3dt51053k

M3 - RGC 21 - Publication in refereed journal

C2 - 23897392

SN - 1477-9226

VL - 42

SP - 13495

EP - 13501

JO - Dalton Transactions

JF - Dalton Transactions

IS - 37

ER -

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

Abstract

Bibliographical note

Funding

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