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This paper describes the stabilization of an intermolecular i-motif by lipophilic modification on the 3′-terminus of oligonucleotides. The hydrophobic aliphatic chain connected at the 3′-terminus of a trinucleotide (dC)3 promoted the formation of an i-motif and significantly enhanced the quadruplex's stability. The impact of lipophilic modification on i-motif's thermal stability was studied by UV-thermal denaturation melting experiments and isothermal titration calorimetry. We found that alkyl chains containing more than 14 carbon atoms could elevate the i-motif structure's stability in a wide range of pH and concentrations.

Graphical abstract: Stabilization of an intermolecular i-motif by lipid modification of cytosine-oligodeoxynucleotides

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