Fluorescent Sensor for the Detection of Alkylating Agents

Description:

Fluorescent Sensor for the Detection of Alkylating Agents

 

Technology: A derivative of pyrene containing methyl salicylate was found to be highly fluorescent and can be used as a sensor for detecting a series of alkylating agents. Inventors at MUSC have developed a salicylic acid derivative, 2-hydroxy-5-[4-(1-pyrenyl methoxy) butoxy] benzoic acid as a turn-on fluorescent sensor for the detection of esterified alkylating agents by fluorescence with maximum emission at 475 nm in solutions at low concentrations. The inventors have designed a turn-on fluorescent probe which utilizes pyrenyl ring and salicylic acid as a donor and acceptor in a FRET based system to generate higher fluorescence to detect alkylating agents effectively. Currently, these types of probes with fluorescence emissions fall within short wavelengths such as  violet and indigo-blue ranges of the electromagnetic spectrum, but the turn-on fluorescent sensor has longest reported wavelength of any fluorescent probe used for alkylators and anti-cancer drugs for robust detection. Alkylating agents such as trimethylsilyl diazomethane, alkyl bromides and iodides, 2-chloroehtyl ethyl sulfide and anti-cancer drugs (busulfan, temezolomide and pipobroman) can be more effectively detected by this invention than other existing fluorescent and non-fluorescent (colorimetric) methods.

Figure. (A) Increase in fluorescence intensity of

4 (10mM at 475nm after reaction with

increasing concentrations of trimethylsilyl

diazomethane (0.10,20,50mM) in DMF/H2O

(9/1, v/v) at 250C for 0.50 hour. (B) Increase in

fluorescence intensity of 4 (6mM at 475nm

after reaction with increasing concentrations

of methyl iodide (0,8,12,16 mM) in DMF in the

presence of TBAF (16mM)at 40oC for 24 hours.

 

Overview: Alkylating agents are synthetic compounds that react with electron rich atoms in molecules to form covalent bonds. They are used as industrial agents, agricultural chemicals and anti-cancer drugs. Alkylating agents are generally toxic and predominantly target bone marrow and the gastro-intestinal tract and some of them cause acute liver or kidney injury as well. Detection of alkylating agents is very important to prevent serious consequences and there are few available techniques to detect them. Fluorescent based probes improve the sensitivity of the detection of alkylating agents but have limitations in human tissues and biological fluids as these probes lose sensitivity and are quenched by biological molecules.

 

Applications: A fluorescent based sensor probe to detect alkylating agents in human tissues and biological fluids to assess whether remediation is necessary following potential exposure to these agents.

 

Advantages: The off-on FRET based fluorescent probe sensitively detects alkylating agents more pronounced and robustly than current fluorescent and non-fluorescent probes available.

 

Keywords: off-on fluorescent probe, alkylating agents, salicylic acid derivative, anti-cancer drugs.

 

Related Publications: Jiang, Y-L. & Broome, A-M. (2017) A novel and versatile fluorescent sensor for the detection of alkylating agents. Bioorganic & Medicinal Chemistry. Under review.

 

Inventors: Ann Marie-Broome and Yu-Lin Jiang

Patent Status: Provisional patent application- filed 11.21.2017.

MUSC FRD Technology ID: P1821P

Licensing Status: Available for licensing

 

 

Patent Information:
Category(s):
Diagnostic
For Information, Contact:
Admin/archive
MUSC Foundation for Research Development
843-876-1900
 
Inventors:
Ann-Marie Broome
Yu-Lin Jiang
Keywords:
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