Noncanonical DNA-binding properties of potential components of an antitumor composition (cytokine AIMP1/p43, lectin SNA, izatizon), which are able to affect different targets

Abstract

Aim. To search the DNA-binding properties of various drugs promising for the creation of the antitumor composition (AIMP1/p43, SNA-I, izatizon), as well as their ability to influence on key matrix processes – DNA transcription and replication, which are a sensitive target for the action of many pharmacological drugs. Methods. The recombinant protein AIMP1/p43 was obtained from supernatant of E.coli lysed cells by metallic chelating chromatography on a Ni‑NTA‑agarose column. Also there were used the elderberry bark lectin SNA-I (LECTINOTEST, Ukraine), and the preparation of own production izatizon (IMBG NAS of Ukraine). The DNA-binding ability of the drugs was investigated by EMSA. As a transcription test system, an enzyme complex of DNA-dependent RNA polymerase of T7 bacteriophage and plasmid DNA pTZ19R * were used. PCR with Taq DNA polymerase and the plasmid pTZ19R * was used as the model replicative system. Results. Experimental conditions, in which the specificity of each drug action appeared, were found: the cytokine AIMP1/p43 and the SNA-I demonstrated the ability to bind to DNA by the EMSA test; izatizon induced structural changes in DNA, blocked the amplification of DNA during the PCR process, and also in vitro transcription with the participation of DNA-dependent RNA polymerase of the bacteriophage T7. Conclusions. Each of the selected drugs, which according to the literature data have antitumor potential, has demonstrated the ability to interact with the model supercoiled plasmid DNA pTZ19R *. The different ways of the selected drugs influence on DNA allows us to expect their effective combined action and synergism in case of their application as a common antitumor composition.
 Keywords: cytokine AIMP1/p43, SNA-I, izatizon, EMSA method, transcription inhibiting, amplification blocking.