A Fmoc-based submonomeric strategy for the solid phase synthesis of optically pure chiral PNAs

Tedeschi, Tullia; Sforza, Stefano; Maffei, Francesca; Corradini, Roberto; Marchelli, Rosangela

doi:10.1016/j.tetlet.2008.05.114

Cited by 9 publications

(3 citation statements)

References 18 publications

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“…Because the starting γ-monomer 4 is stereochemically more stable, its oligomerization results in optically pure products, whereas in the case of the α–monomer ( 5 ) partial racemization during the solid-phase synthesis is possible. To overcome this general problem of α-PNA derivatives, a sub-monomeric approach has been proposed [ 57 – 58 ]; in this approach, carboxymethylated derivatives of the heterocycles are condensed with the pseudopeptide derivative immobilized on the solid phase. Unfortunately, this approach is inapplicable in the case of L -Glu-based monomers 4 and 5.…”

Section: Resultsmentioning

confidence: 99%

Polyanionic Carboxyethyl Peptide Nucleic Acids (ce-PNAs): Synthesis and DNA Binding

et al. 2015

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New polyanionic modifications of polyamide nucleic acid mimics were obtained. Thymine decamers were synthesized from respective chiral α- and γ-monomers, and their enantiomeric purity was assessed. Here, we present the decamer synthesis, purification and characterization by MALDI-TOF mass spectrometry and an investigation of the hybridization properties of the decamers. We show that the modified γ-S-carboxyethyl-T10 PNA forms a stable triplex with polyadenine DNA.

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Section: Resultsmentioning

confidence: 99%

Polyanionic Carboxyethyl Peptide Nucleic Acids (ce-PNAs): Synthesis and DNA Binding

et al. 2015

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“…A variety of organocatalysts, complexes of transition metals or boron, tin and silicon reagents are available for this reaction. We selected sodium cyanoborohydride (NaBH 3 CN) as a suitable reagent due to its earlier applications for reductive alkylation reaction in amino acid chemistry and/ or peptide chemistry [ 29 – 33 ]. N 2 -Boc-2,4-diamino-butanoic acid ( 10 ) was subjected to a reductive amination reaction with aldehyde 7 at room temperature in a solvent mixture of acetic acid/ methanol (1:99, v/v) where NaBH 3 CN was used as the catalyst for the reaction ( Fig 3 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Triamino Acid Building Blocks with Different Lipophilicities

2015

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To obtain different amino acids with varying lipophilicity and that can carry up to three positive charges we have developed a number of new triamino acid building blocks. One set of building blocks was achieved by aminoethyl extension, via reductive amination, of the side chain of ortnithine, diaminopropanoic and diaminobutanoic acid. A second set of triamino acids with the aminoethyl extension having hydrocarbon side chains was synthesized from diaminobutanoic acid. The aldehydes needed for the extension by reductive amination were synthesized from the corresponding Fmoc-L-2-amino fatty acids in two steps. Reductive amination of these compounds with Boc-L-Dab-OH gave the C4-C8 alkyl-branched triamino acids. All triamino acids were subsequently Boc-protected at the formed secondary amine to make the monomers appropriate for the N-terminus position when performing Fmoc-based solid-phase peptide synthesis.

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“…The main strategies proposed to solve the first problem exploit reductive amination, 17 Mitsunobu reaction, 18 and alkylation of Nosyl- protected amino acids 19 for the synthesis of the chiral backbone, followed by introduction of the carboxymethyl nucleobase. However, the use of complete monomers (i.e., bearing the nucleobase) require careful control of the reaction conditions for the synthesis of C(2)-modified PNAs, as, being α-acilated amino acid derivatives, they are prone to racemization on their chiral center.…”

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

et al. 2021

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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.

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A Fmoc-based submonomeric strategy for the solid phase synthesis of optically pure chiral PNAs

Cited by 9 publications

References 18 publications

Polyanionic Carboxyethyl Peptide Nucleic Acids (ce-PNAs): Synthesis and DNA Binding

Polyanionic Carboxyethyl Peptide Nucleic Acids (ce-PNAs): Synthesis and DNA Binding

Synthesis of Triamino Acid Building Blocks with Different Lipophilicities

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

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