Aim. Oligonucleotides are short fragments of DNA or RNA that play a significant role in many fundamental biological processes and have pharmacological activity [1]. The aim of this study was to investigate the interaction of synthetic purine ribo- and deoxyoligonucleotides (OLNs) with recombinant signaling proteins, in particular interferon α-2b and insulin, their receptors, and somatropin. Conclusions. The results of our experiments indicate that OLNs interact with recombinant signaling proteins and their receptors by different mechanisms (single-, double-ligand positive and negative cooperative) depending on the protein and the ligand itself, which, in turn, may be important for their various therapeutic applications.