Replication of synthetic recognition-encoded oligomers by ligation of trimer building blocks.

ABSTRACT: The development of methods for replication of synthetic information oligomers will underpin the use of directed evolution to search new chemical space. Template-directed replication of triazole oligomers has been achieved using a covalent primer in conjunction with non-covalent binding of complementary building blocks. A phenol primer equipped with an alkyne was first attached to a benzoic recognition unit on a mixed sequence template via selective covalent ester base-pair formation. The remaining phenol recognition units on the template were then used for non-covalent binding of phosphine oxide oligomers equipped with an azide. The efficiency of the templated CuAAC reaction between the primer and phosphine oxide building blocks was investigated as a function of the number of H-bonds formed with the template. Increasing the strength of the non-covalent interaction between the template and the azide lead to a significant acceleration of the templated reaction. For shorter phosphine oxide oligomers intermolecular reactions compete with the templated process, but quantitative templated primer elongation was achieved with a phosphine oxide 3-mer building block that was able to form three H-bonds with the template. NMR spectroscopy and molecular models suggest that the template can fold, but addition of the phosphine oxide 3-mer leads to a complex with three H-bonds between phosphine oxide and phenol groups, aligning the azide and alkyne groups in a favourable geometry for the CuAAC reaction. In the product duplex, ¹H and ³¹P NMR data confirm the presence of the three H-bonded base-pairs, demonstrating that the covalent and non-covalent base-pairs are geometrically compatible. A complete replication cycle was carried out starting from the oligotriazole template by covalent attachment of the primer, followed by template-directed elongation, and hydrolysis of the the ester base-pair in the resulting duplex to regenerate the template and liberate the copy strand. We have previously demonstrated sequence-selective oligomer replication using covalent base-pairing, but the trimer building block approach described here is suitable for replication of sequence information using non-covalent binding of the monomer building blocks to a template.

SUBMITTER: Nunez-Villanueva D 

PROVIDER: S-EPMC10661083 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature