Nonenzymatic polymerase-like template-directed synthesis of acyclic l-threoninol nucleic acid

Keiji Murayama (), Hikari Okita, Takumi Kuriki and Hiroyuki Asanuma ()
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Keiji Murayama: Nagoya University
Hikari Okita: Nagoya University
Takumi Kuriki: Nagoya University
Hiroyuki Asanuma: Nagoya University

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract Evolution of xeno nucleic acid (XNA) world essentially requires template-directed synthesis of XNA polymers. In this study, we demonstrate template-directed synthesis of an acyclic XNA, acyclic l-threoninol nucleic acid (l-aTNA), via chemical ligation mediated by N-cyanoimidazole. The ligation of an l-aTNA fragment on an l-aTNA template is significantly faster and occurs in considerably higher yield than DNA ligation. Both l-aTNA ligation on a DNA template and DNA ligation on an l-aTNA template are also observed. High efficiency ligation of trimer l-aTNA fragments to a template-bound primer is achieved. Furthermore, a pseudo primer extension reaction is demonstrated using a pool of random l-aTNA trimers as substrates. To the best of our knowledge, this is the first example of polymerase-like primer extension of XNA with all four nucleobases, generating phosphodiester bonding without any special modification. This technique paves the way for a genetic system of the l-aTNA world.

Date: 2021
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DOI: 10.1038/s41467-021-21128-0

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