Chemical Stabilization of Unnatural Nucleotide Triphosphates for the in Vivo Expansion of the Genetic Alphabet.

ABSTRACT: We have developed an unnatural base pair (UBP) and a semisynthetic organism (SSO) that imports the constituent unnatural nucleoside triphosphates and uses them to replicate DNA containing the UBP. However, propagation of the UBP is at least in part limited by the stability of the unnatural triphosphates, which are degraded by cellular and secreted phosphatases. To circumvent this problem, we now report the synthesis and evaluation of unnatural triphosphates with their β,γ-bridging oxygen replaced with a difluoromethylene moiety, yielding dNaMTP^CF2 and dTPT3TP^CF2. We find that although dNaMTP^CF2 cannot support in vivo replication, likely due to poor polymerase recognition, dTPT3TP^CF2 can, and moreover, its increased stability can contribute to inc

SUBMITTER: Feldman AW 

PROVIDER: S-EPMC5325089 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature