The present invention provides a method for preparing a modified nucleic acid molecule comprising a nucleic acid portion and a non-nucleic acid portion by reacting a first reactant with a second reactant, wherein the first reactant comprises In connection with the above method, wherein the second reactant is an amino-modified nucleic acid molecule comprising a non-nucleic acid portion and a carboxyl group, and wherein the second reactant is an amino-modified nucleic acid molecule comprising the nucleic acid portion and an amino-modified portion comprising an amino group linked to the nucleic acid portion. Comprises: a) activating a first reactant, preferably a carboxyl group of the first reactant, with a condensing reagent in a water-miscible organic solvent; and b) the activated first reaction of step a). Amino modification of an amino-modified nucleic acid molecule dissolved in a substance, preferably an activated carboxyl group of a first reactant, and a second reactant, preferably in water, or a mixture of a water-miscible organic solvent and water. Department And a step of reacting an amino group, which nucleic acid molecules modified by is formed.
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