Affiliation:
1. Department of Organic Chemistry NCCR Chemical Biology Faculty of Science University of Geneva CH-1211 Geneva Switzerland
Abstract
AbstractThe exceptional hybridization properties of peptide nucleic acids (PNAs) coupled with the ease of their synthesis has made this artificial nucleic acid mimetic a desirable platform for diagnostics, therapeutics and supramolecular engineering. PNA backbone modifications have been extensively explored to finetune physicochemical properties and for conjugation of functional molecules. Here, we detail the synthesis of a universal γ‐propargyl‐PNA backbone from serine, and its acylation with the four DNA canonical nucleobases. The availability of serine as d or l enantiomer provide simple accesses to PNA oligomers for hybridization with natural oligonucleotides or for orthogonal hybridization circuitry. We show that late‐stage conjugation enables optimization of the physicochemical properties. This approach is appealing due to its orthogonality to Fmoc‐SPPS, its flexibility and ease for introducing diversity by on‐resin copper(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC). We exemplified the utility of these novel monomers with PNA based hybridization chain reactions (HCRs).
Funder
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
National Center of Competence in Research Chemical Biology
European Molecular Biology Organization
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Drug Discovery,Biochemistry,Catalysis