Synthesis 2021; 53(23): 4440-4448
DOI: 10.1055/a-1538-9883
paper

New Cleavable Spacers for Tandem Synthesis of Multiple Oligo­nucleotides

Kazuki Yamamoto
,
Yasufumi Fuchi
,
Masaya Okabe
,
Takashi Osawa
,
Yuta Ito
,
K.Y. acknowledges a Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan.


Abstract

In solid-phase oligonucleotide synthesis, a single oligonucleotide is generally acquired from a column loaded with a specific solid support. Herein, we have developed new cleavable spacer (CS) derivatives for tandem synthesis of multiple oligonucleotides on a single column­. Four CS analogues were designed, synthesized, and inserted between two oligonucleotide sequences using an automated oligonucleotide synthesizer. The CS derivatives bearing a cyclic cis-1,2-diol exhibited efficient release of the two oligonucleotides under commonly employed basic conditions of aqueous ammonia. Among the CS analogues, it was found that CS with a robust structure can potentially be applied as a spacer molecule in the tandem synthesis of multiple oligonucleotides in a single sequence.

Supporting Information



Publication History

Received: 31 May 2021

Accepted after revision: 28 June 2021

Accepted Manuscript online:
28 June 2021

Article published online:
02 August 2021

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