The substrate specificity of recombinant full-length diguanylate cyclase (DGC) of Thermotoga maritima with mutant allosteric site was investigated. It has been originally shown that the enzyme could use GTP closest analogues - 2'-deoxyguanosine-5'-triphosphate (dGTP) and 9-β-D-arabinofuranosyl-guanine-5'-triphosphate (araGTP) as the substrates. The first demonstrations of an enzymatic synthesis of bis-(3'-5')-cyclic dimeric deoxyguanosine monophosphate (c-di-dGMP) and the previously unknown bis-(3'-5')-cyclic dimeric araguanosine monophosphate (c-di-araGMP) using DGC of T. maritima in the form of inclusion bodies have been provided.
The present study is focused on the first attempt to use an enzymatically produced biological preparation of cyclic diguanosine monophosphate (cyclic di-GMP) for the therapy of animal cancer. Feline breast carcinoma was chosen as the test model. The preparation was administered intratumorally to induce the immunogenic death of a part of the cancer cells and thus carry out the so-called in situ antitumor vaccination. Preliminary results indicate good therapeutic prospects of studied biopreparation for animal cancer treatment.
In conclusion, the expedience of further trials of cyclic di-GMP preparation for in situ antitumor vaccination was stated. The need to supplement this mono-preparation with another immunostimulating adjuvant characterized by a mechanism of action distinct from that exhibited by cyclic di-GMP was emphasized. DNA preparation comprising the so-called immunostimulating CpG motifs was provided as an example of such compound.
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