Over the past decades, peptide nucleic acid/DNA (PNA:DNA) duplex stability has been improved via backbone modification, often achieved via introducing an amino acid side chain at the α- or γ-position in the PNA sequence. It was previously shown that interstrand cross-linking can further enhance the binding event. In this work, we combined both strategies to fine-tune PNA crosslinking towards single stranded DNA sequences using a furan oxidation-based crosslinking method; for this purpose, γ-L-lysine and γ-L-arginine furan-PNA monomers were synthesized and incorporated in PNA sequences via solid phase synthesis. It was shown that the L-lysine γ-modification had a beneficial effect on crosslink efficiency due to pre-organization of the PNA helix and a favorable electrostatic interaction between the positively-charged lysine and the negatively-charged DNA backbone. Moreover, the crosslink yield could be optimized by carefully choosing the type of furan PNA monomer. This work is the first to describe a selective and biocompatible furan crosslinking strategy for crosslinking of γ-modified PNA sequences towards single-stranded DNA.

Synthesis and improved cross-linking properties of c5-modified furan bearing pnas / Elskens, Joke; Manicardi, Alex; Costi, Valentina; Madder, Annemieke; Corradini, Roberto. - In: MOLECULES. - ISSN 1420-3049. - 22:11(2017), p. 1. [10.3390/molecules22112010]

Synthesis and improved cross-linking properties of c5-modified furan bearing pnas

Manicardi, Alex;COSTI, VALENTINA;Corradini, Roberto
2017

Abstract

Over the past decades, peptide nucleic acid/DNA (PNA:DNA) duplex stability has been improved via backbone modification, often achieved via introducing an amino acid side chain at the α- or γ-position in the PNA sequence. It was previously shown that interstrand cross-linking can further enhance the binding event. In this work, we combined both strategies to fine-tune PNA crosslinking towards single stranded DNA sequences using a furan oxidation-based crosslinking method; for this purpose, γ-L-lysine and γ-L-arginine furan-PNA monomers were synthesized and incorporated in PNA sequences via solid phase synthesis. It was shown that the L-lysine γ-modification had a beneficial effect on crosslink efficiency due to pre-organization of the PNA helix and a favorable electrostatic interaction between the positively-charged lysine and the negatively-charged DNA backbone. Moreover, the crosslink yield could be optimized by carefully choosing the type of furan PNA monomer. This work is the first to describe a selective and biocompatible furan crosslinking strategy for crosslinking of γ-modified PNA sequences towards single-stranded DNA.
Synthesis and improved cross-linking properties of c5-modified furan bearing pnas / Elskens, Joke; Manicardi, Alex; Costi, Valentina; Madder, Annemieke; Corradini, Roberto. - In: MOLECULES. - ISSN 1420-3049. - 22:11(2017), p. 1. [10.3390/molecules22112010]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2836691
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