Traditional oligodeoxynucleotide (ODN) synthesis methods use strong basic and nucleophilic conditions for deprotection and cleavage of ODN from solid-support. Therefore, the synthesis of ODNs containing sensitive functional groups cannot be achieved by traditional synthesis methods. To overcome this challenge, Dim-Dmoc technology was developed which uses Dim and Dmoc groups (1,3-dithian-2-yl-methyl based functions used for phosphate and amine protection) for the solid phase ODN synthesis. To further enhance this technology, we propose the use of methyl-substituted Dim-Dmoc groups which require non-nucleophilic and weakly basic conditions for deprotection and cleavage of the ODN. As a result, the methyl-substituted Dim-Dmoc technology will be suitable for the synthesis of sensitive ODN analogs that have a wide range of applications. To demonstrate the feasibility of the methyl-substituted Dim-Dmoc technology, various methyl-substituted Dim-Dmoc protected ODNs were synthesized, deprotected and cleaved under mild conditions, purified with RP HPLC, and characterized with MALDI-TOF MS.

Solid-phase oligodeoxynucleotide synthesis using methyl-substituted Dim and Dmoc as phosphate and amine protecting groups

ACS Spring Meeting 2021

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