Premium
Substitution‐Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex‐Forming Templates
Author(s) -
Malina Jaroslav,
Farrell Nicholas P.,
Brabec Viktor
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201803448
Subject(s) - dna , chemistry , triple helix , intercalation (chemistry) , dna clamp , dna polymerase , pyrimidine , polymerase , stereochemistry , biophysics , biochemistry , gene , polymerase chain reaction , biology , inorganic chemistry , reverse transcriptase
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.