**3.3 Effect of 2-5A fluorodeoxyanalogs on macrophage phagocytic activity**

Another type of immune cells, mononuclear phagocytes (MPs) are cells, which are directly engaged in the formation of humoral and cellular immune responses. Their


*\*One lytic unit was assumed equal to the number of effector cell (natural killers) lysing 20% (LU20), 30% (LU30), and 50% (LU50), respectively, of target cells during the study period. K-562 erythroleukemia cells were used as target cells and labeled with a non-radioactive chelate complex of europium diethylenetriaminepentaacetate (EuDTPA). \*\*The percentage of increased lytic activity of N-lymphocytes was calculated by the formula: {[(LE/106 treated cells/ LE/106 control cells)] - 1} x 100.*

## **Table 1.**

*Effect of 3*′*-fluorodeoxyanalogs on NK-lymphocyte activity.*

phagocytic activity entailing absorption and killing of certain types of microorganisms is one of many results of MP functioning.

The study of the effect of 2-5A on MPs showed that 2-5A analogs should have three phosphate residues at the 5′-end and at least three adenosine moieties to increase macrophage phagocytic activity. Moreover, it was found that MPs of various animal species have a 2-5A receptor, which has a high specificity. Substitution of adenosine moiety for inosine did not contribute to binding to the 2-5A receptor and thus did not increase macrophage phagocytic activity [45, 46].


*Values shown have been obtained from six to nine independent experiments. The phagocytic activity of macrophages was expressed in terms of the chemiluminescence index:* ( ) <sup>−</sup> = ⋅ 2 1 1 *CL* % <sup>100</sup> *CL CL <sup>I</sup> CL , where CL1 is the maximum chemiluminescence (mV) of native P388D1 cells and CL2 is the maximum chemiluminescence (mV) of activated P388D1 cells.*

#### **Table 2.**

*Effect of fluorodeoxyanalogs 2-5Aa on the phagocytic activity of mouse macrophages of the P388D1 line.*

*Modified (2*′*,5*′*)Oligonucleotides: The Influence of Structural and Steriochemical Factors… DOI: http://dx.doi.org/10.5772/intechopen.108630*

It was demonstrated that all 2-5A *ribo*-fluorodeoxyanalogs were much more superior in activating P388D1 cells than *xylo*-analogs, and the parent oligomer [47, 48]. Probably, *anti-*conformation of the heterocyclic base with the dominant S-conformation of carbohydrate moieties is more preferable for 2-5A receptor of P388D1 cells compared to the parent trimer where the furanose ring is located in the dynamic S↔N equilibrium with prevalent *anti*-orientation of adenine bases [31]. Conformational rigidity of the carbohydrate ring of the xylonucleoside, AF , which was found to be largely occupied in *N*-conformation along with *syn*-orientation of the base resulted in reduced activation of P388D1 cells induced by (2′-5′) oligoadenylates. However, significant differences exist between *xylo-*and *ribo*-analogs in their ability to increase phagocytic activity (**Table 2**).
