Open AccessSubmonomeric Strategy with Minimal Protection for the Synthesis of C(2)-Modified Peptide Nucleic Acids
Author(s) -
Stefano Volpi,
Andrea Rozzi,
Nicola Rivi,
Martieri,
Wolfgang Knoll,
Roberto Corradini
Publication year - 2021
Publication title -
organic letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.94
H-Index - 239
eISSN - 1523-7060
pISSN - 1523-7052
DOI - 10.1021/acs.orglett.0c04116
Subject(s) - chemistry , nucleic acid , combinatorial chemistry , peptide nucleic acid , peptide , dna , selectivity , mutant , stereochemistry , gene , biochemistry , catalysis
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.