TITLE:
Primer-Like Inhibitors for DNA Repair Enzymes of the AML-HL60 and WERI-1A/Y79 Malignant Cells
AUTHORS:
Sergei V. Stovbun, Kirill V. Ermakov, Alexander A. Bukhvostov, Alexander S. Vedenkin, Dmitry A. Kuznetsov
KEYWORDS:
Magnetic Isotope Effects (MIE), DNA Repair, DNA Polymerases, DNA-Enzyme Binding
JOURNAL NAME:
Advances in Enzyme Research,
Vol.7 No.3,
September
27,
2019
ABSTRACT: A conventionally synthesized thio- and cyano-modified
single-stranded poly(dNTP) sequences of different molecular sizes
(20n - 200n) and the same lengths routine poly(dNTP) and poly(NTP) species were
obtained through the good services provided
by the Russian Federal Bioorganic Products Group and by the
ThermoFischer, Inc., and then tested for their impact on catalytic activities
of β-like DNA polymerases from chromatin of HL-60, WERI-1A and Y-79 cells as well as for the affinity patterns in
DNApolβ-poly(dNTP)/ (NTP) pairs, respectively. An essential link between the lengths of
ultrashort (50n - 100n) single-stranded poly(dNTP) sequences of different structures and their
inhibitory effects towards the cancer-specific DNA polymerases β has been found. A possible significance of this phenomenon for both DNA
repair suppression in tumors and a consequent anti-cancer activity of the DNA
repair related short poly(dNTP) fragments has been for the first time
emphasized with a respect to their pharmacophore revealing potential. Thus,
this work presents an experimental attempt to upgrade a contemporary attitude
towards the DNA derived products applied for anti-cancer agenda, particularly, for acute myeloid leukemia and
retinoblastoma cell DNA repair machinery breakdown. In this study, tumor
specific DNA polymerases β were found
of being the targets for attack promoted with the primer-like single-stranded DNA fragments followed by consequent
cytostatic phenomena. A novel concept of the DNA related anti-cancer medicines
is under discussion.