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Direct Fluorimetric Readout Assay of Human RNR-α Oligomerization

详细技术说明

This invention describes a method foridentifying the monomer alpha (α) of human ribonucleotide reductase (hRNR) atits different states of oligomerization, for diagnosis and treatment of cancerand leukemia.

*Abstract

hRNR is an enzyme that supplies the dNTPs required for DNAreplication and repair. It plays a central role in cell synthesis, growth, andmetastasis of cancer cells. Its identification relies on thehexamerization-induced fluorescence quenching of hRNR-α to report hRNRinhibition.

Potential Applications

• High-throughput screening of compounds inhibiting RNR for treatment of cancer and leukemia;
• Since RNR activity positively correlated with cancer cell proliferation, the method can be used as a direct readout assay that reports on the inhibited state of RNRs for:
  • Diagnosis and prognosis of cancer and leukemia;
  • Determination of susceptibility to therapeutic drugs.

Advantages

• Highly sensitive and rapid readout of hRNR inhibition;
• Not activity-based assay so do not require β subunit with a short half-life (20’) in vitro;
• Able to distinguish α-activation state (dimer) from α-inhibited state (hexamer);
• Uncoupled to any other enzymes;
• Fluorescent substrates instead of radio-labeled substrates;
• Screening of nucleotide-based and/or non-nucleotide-based compounds for targeted therapy;
• Adaptable to mammalian system.

*Licensing

CarolynTheodore607-254-4514cat42@cornell.edu

其他

Yimon Aye; Yuan Fu; Hongyu Lin; Somsinee Wisitpitthaya; William Blessing, A Fluorimetric Readout Reporting the Kinetics of Nucleotide-Induced Human Ribonucleotide Reductase Oligomerization, ChemBioChem (2014)

国家/地区

美国