Modified nucleotides and nucleotide conjugates for polynucleotide synthesis

Abstract

Disclosed herein are improved methods for the de novo synthesis of nucleic acids by cyclic extension using a template-independent polymerase. Secondary structure formation in the nascent chain, which may inhibit extension reactions, is suppressed by the use of monomers with O-alkylated nucleobases that prevent Watson-Crick base pairing and/or other structures. After the synthesis is completed, the nucleobases can be converted back into native form by enzymatic removal of the alkyl groups.

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