TY - JOUR

T1 - DNA Conformational Changes Induced by Its Interaction with Binuclear Platinum Complexes in Solution Indicate the Molecular Mechanism of Platinum Binding

AU - Соколов, Петр Александрович

AU - Касьяненко, Нина Анатольевна

AU - Бакулев, Владимир Михайлович

N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - Platinum anticancer drugs inhibit the division of cancer cells through a DNA binding mechanism. The bimetallic platinum compounds have a possibility for blocking DNA replication via the cross-linking of DNA functional groups at different distances. Many compounds with metals of the platinum group have been tested for possible antitumor activity. The main target of their biological action is a DNA molecule. A combined approach to the study of the interaction of DNA with biologically active compounds of this type is proposed. The capabilities of various methods (hydrodynamic, spectral, microscopy) in obtaining information on the type of binding of coordination compounds to DNA are compared. The analysis of DNA binding with platinum binuclear compounds containing pyrazine, tetrazole, 5-methyltetrazole, 3-propanediamine as bridging ligands in a solution was carried out with the methods of circular dichroism (CD), luminescent spectroscopy (LS), low gradient viscometry (LGV), flow birefringence (FB) and atomic force microscopy (AFM). The competitive binding of different platinum compounds to DNA and the analysis of platinum attachment to DNA after protonation of its nitrogen bases simply indicates the involvement of N7 guanine in binding. Fluorescent dye DAPI was also used to recognize the location of platinum compounds in DNA grooves. DNA conformational changes recorded by variations in persistent length, polyelectrolyte swelling, DNA secondary structure, and its stability clarify the molecular mechanism of the biological activity of platinum compounds.

AB - Platinum anticancer drugs inhibit the division of cancer cells through a DNA binding mechanism. The bimetallic platinum compounds have a possibility for blocking DNA replication via the cross-linking of DNA functional groups at different distances. Many compounds with metals of the platinum group have been tested for possible antitumor activity. The main target of their biological action is a DNA molecule. A combined approach to the study of the interaction of DNA with biologically active compounds of this type is proposed. The capabilities of various methods (hydrodynamic, spectral, microscopy) in obtaining information on the type of binding of coordination compounds to DNA are compared. The analysis of DNA binding with platinum binuclear compounds containing pyrazine, tetrazole, 5-methyltetrazole, 3-propanediamine as bridging ligands in a solution was carried out with the methods of circular dichroism (CD), luminescent spectroscopy (LS), low gradient viscometry (LGV), flow birefringence (FB) and atomic force microscopy (AFM). The competitive binding of different platinum compounds to DNA and the analysis of platinum attachment to DNA after protonation of its nitrogen bases simply indicates the involvement of N7 guanine in binding. Fluorescent dye DAPI was also used to recognize the location of platinum compounds in DNA grooves. DNA conformational changes recorded by variations in persistent length, polyelectrolyte swelling, DNA secondary structure, and its stability clarify the molecular mechanism of the biological activity of platinum compounds.

KW - 1,3-propanediamine

KW - DNA-platinum complexes

KW - binuclear platinum (II) compounds

KW - pyrazine

KW - tetrazole

UR - http://www.scopus.com/inward/record.url?scp=85130816970&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/497551e8-bc83-3d03-8100-0e43810cd1f1/

U2 - 10.3390/polym14102044

DO - 10.3390/polym14102044

M3 - Article

C2 - 35631926

VL - 14

JO - Polymers

JF - Polymers

SN - 2073-4360

IS - 10

M1 - 2044

ER -