<i>De novo</i>
            synthesis and development of an RNA enzyme

Yoshiya Ikawa, Kentaro Tsuda, Shigeyoshi Matsumura, Tan Inoue

doi:10.1073/pnas.0405886101

<jats:p> Arbitrary manipulation of molecular recognition at the atomic level has many applications. However, systematic design and <jats:italic>de novo</jats:italic> synthesis of an artificial enzyme based on such manipulation has been a long-standing challenge in the field of chemistry and biotechnology. In this report, we developed an artificial RNA ligase by implementing a synthetic strategy that fuses a series of 3D molecular modelings based on naturally occurring RNA–RNA recognition motifs with a small-scale combinatorial synthesis of a modular catalytic unit. The resulting ligase produces a 3′–5′ linkage in a template-directed manner for any combinations of two nucleotides at the reaction site. The reaction rate is 10 <jats:sup>6</jats:sup> -fold over that of the uncatalyzed reaction with a yield higher than those of previously reported ligase ribozymes. The strategy may be applicable to the synthesis and development of a variety of nonnatural functional RNAs with defined 3D structures. </jats:p>

<i>De novo</i> synthesis and development of an RNA enzyme

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