The Nature: Scientific Reports published another joint study on the screening of antitumor drugs from the Laboratory of Nano-Bioengineering of NRNU MEPhI and two French research groups

A paper by Professor Igor Nabiev, the leading scientist of the Laboratory of Nano-Bioengineering, and his French colleagues from the universities of Reims and Nantes (Lafont, F., Ayadi, N., Charlier, C., Weigel, P., Nabiev, I., Benhelli-Mokrani, H, Fleury, F. Assessment of DNA-PKcs kinase activity by quantum dot–based microarray) came out in the Nature: Scientific Reports, a top-rated international journal. The study deals with a new approach to screening a class of potential sensitizers of antitumor therapy. The paper is available in Open Access at the journal's website >>.

The publication describes the development and testing of a microarray for quick and precise estimation of the cell content and, more importantly, degree of phosphorylation of the protein substrates of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and, indirectly the activity of DNA-PKcs itself.

Why is this important?

Many malignant tumors are resistant to chemo- and radiotherapies damaging the DNA of cancer cells because of the mechanisms for repairing DNA lesions, which normally prevent genetic defects. DNA-PKcs triggers one of the main mechanisms of DNA repair when DNA has been damaged. This enzyme starts working in response to the appearance of double-strand breaks in DNA to initiate (via phosphorylation) the activities of a series of other enzymes, which "heal" the lesion. Inhibitors of this key enzyme are used to suppress the "healing" of cancer cells and thereby make the anticancer therapy more efficacious. To select the most effective inhibitors, one has to know how the activity of DNA-PKcs (or the degree of phosphorylation of the proteins it activates) can be estimated and the changes in its activity in cancer cells monitored. It is particularly important that this analysis should be quick, because there are lots of potential inhibitors to be screened.

The microarray developed by the authors is a tool to fulfill this task. The main difference of the new microarray from the currently available methods is that, instead of the classical organic fluorescent labels, it employs quantum dots, semiconductor nanocrystals with many times brighter fluorescence and resistance to photobleaching. In addition, quantum dots have very narrow fluorescence spectra, while their absorption spectra are wide. This allows the researcher to simultaneously detect signals from many labels for different targets; i.e., the analysis throughput is substantially enhanced.

The authors have tested the newly developed microarray on replication protein A, one of the DNA-PKcs substrates, to demonstrate that their approach indeed allow the degrees of protein phosphorylation at different amino acid residues to be estimated with a high precision and the DNA-PKcs activity in cells to be measured. Hence, the new microarray is an efficient tool for screening the potential inhibitors of this enzyme.

It is worth noting that, since protein phosphorylation is a versatile mechanism of regulation of various enzyme activities in cells, the microarrays based on the approach suggested by the NRNU MEPhI's and French researchers have potential uses far beyond those shown in their paper.

Nature: Scientific Reports is an international journal publishing original research papers from various fields of science and medicine. The journal is included in the first quartile of interdisciplinary journals according to the JCR rating and is among the best in the Interdisciplinary Journals category.

Contacts:

Professor Igor R. Nabiev, Ph.D., D.Sci., leading scientist (igor.nabiev@gmail.com)

Maria G. Korenkova, director of external relations (MGKorenkova@mephi.ru)

Laboratory of Nano-Bioengineering, Moscow Engineering Physics Institute
31 Kashirskoe shosse, 115409 Moscow, Russian Federation
http://www.lnbe.mephi.ru/en

 
 
 
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