Japan Science and Technology Agency

Hideto Maruyama

Hiroshi Abe

Yoshihiro Ito

A non-enzymatic method is provided for binding a first nucleic acid chain to a second nucleic acid chain without introducing a sulfur atom into the combined nucleic acid chain, the method comprising reacting a first nucleic acid chain having a phosphorothioate group at the 3' or 5&#x2032; terminus with a second nucleic acid chain having a hydroxyl group or an amino group at the 3&#x2032; or 5&#x2032; terminus in the presence of an electrophile that has a leaving group and is configured to leave the leaving group and bind to a sulfur atom of the phosphorothioate group of the first nucleic acid chain at the site to which the leaving group had been bound, and remove the sulfur atom from the phosphorothioate group of the first nucleic acid chain and a hydrogen atom from the hydroxyl group or from the amino group of the second nucleic acid chain via a nucleophilic substitution with an oxygen atom of the hydroxyl group or a nitrogen atom of the amino group of the second nucleic acid chain, and thereby form a bond between a phosphorus atom of the phosphate group of the first nucleic acid chain and the oxygen atom or the nitrogen atom of the second nucleic acid chain. Examples of structures produced by the binding method are shown below. 

Method for non-enzymatic combination of nucleic acid chains

A method for constructing a functional nucleic acid molecule comprising 1 or 2 nucleic acid strands, wherein 2 or more fragments having at corresponding ends a functional group pair that can mutually couple through a chemical reaction are introduced into a cell, and a functional nucleic acid molecule comprising 1 or 2 nucleic acid strands is formed by ligating mutually the fragments through a reaction between the functional groups in the cell.

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Sapporo, Japan

Hideto Maruyama