Substitution-Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex-Forming Templates.
Angew Chem Int Ed Engl
; 57(28): 8535-8539, 2018 07 09.
Article
em En
| MEDLINE
| ID: mdl-29766623
ABSTRACT
The formation of triple-helical DNA is implicated in the regulation of gene expression. The triplexes are, however, unstable under physiological conditions so that effective stabilizers for the triplex formation are needed. Herein, we describe a new strategy for the stabilization of such triplexes that is based on antitumor substitution-inert polynuclear platinum complexes (SI-PPCs). These compounds were previously shown to bind to DNA through the phosphate clamp-a discrete mode of DNA-ligand recognition distinct from the canonical intercalation and minor-groove binding. We have found that SI-PPCs efficiently inhibit DNA synthesis by DNA polymerase in sequences prone to the formation of pyrimidine- and purine-motif triplex DNAs. Moreover, the results suggest that SI-PPCs are able to induce the formation of triple-helical DNA between duplexes and strands that are not completely complementary to each other. Collectively, these data provide evidence that SI-PPCs are very efficient stabilizers of triple-stranded DNA that might exert their action by stabilizing higher-order structures such as triple-helical DNA.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
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Polímeros
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DNA
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Inibidores da Síntese de Ácido Nucleico
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DNA Polimerase Dirigida por DNA
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article