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Submonomeric Strategy with Minimal Protection for the Synthesis of C(2)-Modified Peptide Nucleic Acids.

ABSTRACT: A novel synthesis of C(2)-modified peptide nucleic acids (PNAs) is proposed, using a submonomeric strategy with minimally protected building blocks, which allowed a reduction in the required synthetic steps. N(3)-unprotected, d-Lys- and d-Arg-based backbones were used to obtain positively charged PNAs with high optical purity, as inferred from chiral GC measurements. "Chiral-box" PNAs targeting the G12D point mutation of the KRAS gene were produced using this method, showing improved sequence selectivity for the mutated- vs wild-type DNA strand with respect to unmodified PNAs.

SUBMITTER: Volpi S

PROVIDER: S-EPMC7880566 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Submonomeric Strategy with Minimal Protection for the Synthesis of C(2)-Modified Peptide Nucleic Acids.

Volpi Stefano S Rozzi Andrea A Rivi Nicola N Neri Martina M Knoll Wolfgang W Corradini Roberto R

Organic letters 20210108 3

A novel synthesis of C(2)-modified peptide nucleic acids (PNAs) is proposed, using a submonomeric strategy with minimally protected building blocks, which allowed a reduction in the required synthetic steps. N(3)-unprotected, d-Lys- and d-Arg-based backbones were used to obtain positively charged PNAs with high optical purity, as inferred from chiral GC measurements. "Chiral-box" PNAs targeting the G12D point mutation of the <i>KRAS</i> gene were produced using this method, showing improved sequ ...[more]

PMID: 33417460

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