PIM kinase-responsive microsecond-lifetime photoluminescent probes based on selenium-containing heteroaromatic tricycle

Ramesh Ekambaram; Ganesh Babu Manoharan; Erki Enkvist; Kadri Ligi; Stefan Knapp; Asko Uri

doi:10.1039/c5ra20777k

PIM kinase-responsive microsecond-lifetime photoluminescent probes based on selenium-containing heteroaromatic tricycle

Ramesh Ekambaram, Ganesh Babu Manoharan, Erki Enkvist, Kadri Ligi, Stefan Knapp, Asko Uri^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

13 Citations (Scopus)

Abstract

A new structural fragment was synthesized for construction of protein binding-responsive photoluminescent probes. In complex with protein kinases of the PIM family, bisubstrate inhibitors containing benzo[4,5]seleno[3,2-d]pyrimidin-4-one moiety revealed microsecond-lifetime phosphorescence emission after pulse excitation with near-UV radiation. The phosphorescence signal was substantially (more than 50-fold) amplified by a covalently bound fluorescent dye (PromoFluor-555 or PromoFluor-647) whose absorption spectrum well overlapped with the phosphorescence emission spectrum of the selenium-containing heteroaromatic tricycle. The developed organic small-molecule long-lifetime photoluminescence probes possess subnanomolar affinity towards kinases of the PIM family and reveal especially strong emission signal with PIM-2 isozyme. The developed probes have potential to be used for monitoring of activity of PIM kinases for diagnosis of cancer.

Original language	English
Pages (from-to)	96750-96757
Number of pages	8
Journal	RSC Advances
Volume	5
Issue number	117
DOIs	https://doi.org/10.1039/c5ra20777k
Publication status	Published - 5 Nov 2015
Externally published	Yes

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title = "PIM kinase-responsive microsecond-lifetime photoluminescent probes based on selenium-containing heteroaromatic tricycle",

abstract = "A new structural fragment was synthesized for construction of protein binding-responsive photoluminescent probes. In complex with protein kinases of the PIM family, bisubstrate inhibitors containing benzo[4,5]seleno[3,2-d]pyrimidin-4-one moiety revealed microsecond-lifetime phosphorescence emission after pulse excitation with near-UV radiation. The phosphorescence signal was substantially (more than 50-fold) amplified by a covalently bound fluorescent dye (PromoFluor-555 or PromoFluor-647) whose absorption spectrum well overlapped with the phosphorescence emission spectrum of the selenium-containing heteroaromatic tricycle. The developed organic small-molecule long-lifetime photoluminescence probes possess subnanomolar affinity towards kinases of the PIM family and reveal especially strong emission signal with PIM-2 isozyme. The developed probes have potential to be used for monitoring of activity of PIM kinases for diagnosis of cancer.",

author = "Ramesh Ekambaram and Manoharan, {Ganesh Babu} and Erki Enkvist and Kadri Ligi and Stefan Knapp and Asko Uri",

note = "Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2015",

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T1 - PIM kinase-responsive microsecond-lifetime photoluminescent probes based on selenium-containing heteroaromatic tricycle

AU - Ekambaram, Ramesh

AU - Manoharan, Ganesh Babu

AU - Enkvist, Erki

AU - Ligi, Kadri

AU - Knapp, Stefan

AU - Uri, Asko

PY - 2015/11/5

Y1 - 2015/11/5

N2 - A new structural fragment was synthesized for construction of protein binding-responsive photoluminescent probes. In complex with protein kinases of the PIM family, bisubstrate inhibitors containing benzo[4,5]seleno[3,2-d]pyrimidin-4-one moiety revealed microsecond-lifetime phosphorescence emission after pulse excitation with near-UV radiation. The phosphorescence signal was substantially (more than 50-fold) amplified by a covalently bound fluorescent dye (PromoFluor-555 or PromoFluor-647) whose absorption spectrum well overlapped with the phosphorescence emission spectrum of the selenium-containing heteroaromatic tricycle. The developed organic small-molecule long-lifetime photoluminescence probes possess subnanomolar affinity towards kinases of the PIM family and reveal especially strong emission signal with PIM-2 isozyme. The developed probes have potential to be used for monitoring of activity of PIM kinases for diagnosis of cancer.

AB - A new structural fragment was synthesized for construction of protein binding-responsive photoluminescent probes. In complex with protein kinases of the PIM family, bisubstrate inhibitors containing benzo[4,5]seleno[3,2-d]pyrimidin-4-one moiety revealed microsecond-lifetime phosphorescence emission after pulse excitation with near-UV radiation. The phosphorescence signal was substantially (more than 50-fold) amplified by a covalently bound fluorescent dye (PromoFluor-555 or PromoFluor-647) whose absorption spectrum well overlapped with the phosphorescence emission spectrum of the selenium-containing heteroaromatic tricycle. The developed organic small-molecule long-lifetime photoluminescence probes possess subnanomolar affinity towards kinases of the PIM family and reveal especially strong emission signal with PIM-2 isozyme. The developed probes have potential to be used for monitoring of activity of PIM kinases for diagnosis of cancer.

UR - http://www.scopus.com/inward/record.url?scp=84946935057&partnerID=8YFLogxK

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DO - 10.1039/c5ra20777k

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VL - 5

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EP - 96757

JO - RSC Advances

JF - RSC Advances

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ER -

PIM kinase-responsive microsecond-lifetime photoluminescent probes based on selenium-containing heteroaromatic tricycle

Abstract

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