Design and Synthesis of 2-Functionalised Oligonucleotides. Their Application for Covalent Trapping the Protein – DNA Complexes

Toxicity Inspired Cross-Linking for Probing DNA–Peptide Interactions

“…A furan brominated species, resulting from competitive electrophilic aromatic substitution, is only formed as a minor side product. In the presence of proximal primary amines from amino acid residues, the formed reactive aldehyde functionality generates a Schiff base that can be selectively reduced with NaCNBH 3 to generate a DPC. ,,− , Alternatively, in the case of a differently positioned furan as shown in earlier work focusing on interstrand cross-linking, − stable adducts can be formed with proximal nucleic acid bases, generating ICLs. It is clear that carefully planned differential positioning of the furan moiety on the nucleoside allows switching from ICL to DPC formation.…”

“…Finally, obtained DPC yields are in general rather low (10−20%). 6 In order to probe the DNA−protein interface, use of a cross-linking mechanism requiring the presence of proximal nucleophilic side chain functionalities can be considered as a viable alternative.…”

“…Further, due to the occurrence of high-energy intermediates, the resulting structures are not always representative of the actual structure in the absence of the cross-link. Finally, obtained DPC yields are in general rather low (10–20%) . In order to probe the DNA–protein interface, use of a cross-linking mechanism requiring the presence of proximal nucleophilic side chain functionalities can be considered as a viable alternative.…”

Modified Oligonucleotides: New Structures, New Properties, and New Spheres of Application

“…It is always important to remember that one of the fundamental properties of oligonucleotides is their capability of complementary interactions; therefore, when various modifications are introduced, one of the main tasks is to preserve the structures and functions necessary for interaction with complementary regions of target nucleic acids. It is no coincidence that the modification in most cases is aimed at the sugar phosphate backbone [13][14][15][16][17][18]. Important aspects are an increase in the specificity of binding of modified oligonucleotides to target nucleic acids or NA-binding proteins and an increase in the stability of these compounds with respect to hydrolysis by cellular nucleases.…”