The review addresses simple and efficient approaches to the rational synthesis of conjugates of oligonucleotides with functional molecules (FMs), including active low-molecular-weight compounds and macromolecules of various natures. These compounds can possess high reactivity, catalytic activity, or affinity for nucleic acid (NA) targets (e.g., intercalators, ligands exhibiting NA affinity); they can provide visualization (reporter groups, fluorophores), intracellular transport, desired cellular distribution, and related functions. The principles of "oligonucleotide construction set" are formulated as an algorithm taking account of specific features of conjugate formation depending on the structure of both the nucleic acid component and the FM component in terms of the pre-synthetic (direct) and postsynthetic (indirect) strategies. Unlike the existing reviews, which are most often devoted to one or a few conjugation techniques or conjugates of a particular type, the present review demonstrates the whole diversity of interactions between oligonucleotides and various compounds. The review covers both classic and modern methods that employ a minimal optimal set of efficient reactions and reagents that make it possible to preserve the functional properties of both components (NA and FM) and achieve the desired action of the conjugate on biological targets. The bibliography includes 420 references.
Meschaninova et al. (2026) studied this question.