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Primer-Like Inhibitors for DNA Repair Enzymes of the AML-HL60 and WERI-1A/Y79 Malignant Cells

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Document pages: 18 pages

Abstract: A conventionally synthesized thio- and cyano-modifiedsingle-stranded poly(dNTP) sequences of different molecular sizes(20n - 200n) and the same lengths routine poly(dNTP) and poly(NTP) species wereobtained through the good services providedby the Russian Federal Bioorganic Products Group and by theThermoFischer, Inc., and then tested for their impact on catalytic activitiesof β-like DNA polymerases from chromatin of HL-60, WERI-1A and Y-79 cells as well as for the affinity patterns inDNApolβ-poly(dNTP) (NTP) pairs, respectively. An essential link between the lengths ofultrashort (50n - 100n) single-stranded poly(dNTP) sequences of different structures and theirinhibitory effects towards the cancer-specific DNA polymerases β has been found. A possible significance of this phenomenon for both DNArepair suppression in tumors and a consequent anti-cancer activity of the DNArepair related short poly(dNTP) fragments has been for the first timeemphasized with a respect to their pharmacophore revealing potential. Thus,this work presents an experimental attempt to upgrade a contemporary attitudetowards the DNA derived products applied for anti-cancer agenda, particularly, for acute myeloid leukemia andretinoblastoma cell DNA repair machinery breakdown. In this study, tumorspecific DNA polymerases β were foundof being the targets for attack promoted with the primer-like single-stranded DNA fragments followed by consequentcytostatic phenomena. A novel concept of the DNA related anti-cancer medicinesis under discussion.

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