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Chiral PNAs with Constrained Open-Chain Backbones

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Peptide Nucleic Acids

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1050))

Abstract

Chiral open-chain PNAs have been shown to have improved properties in terms of control of helical handedness, DNA affinity, sequence selectivity, and cellular uptake. They can be synthesized either using preformed chiral monomers or by means of a submonomeric strategy. The former is preferred when only a stereogenic center is present at C-5, whereas for PNA-bearing substituents at C-2, the submonomeric approach is preferred, since racemization, generally occurring during the solid-phase synthesis, can be minimized by this procedure. Here we describe the protocols for the synthesis of PNA oligomers containing C-2- or C-5- (or both) modified monomers and a GC method for checking the optical purity of C-2-modified PNAs.

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Abbreviations

BTSA:

N,O-Bis(trimethylsilyl)acetamide

CMB:

Carboxymethyl nucleobase

DCC:

N,N-dicyclohexylcarbodiimide

DCM:

Dichloromethane

DIC:

N,N-diisopropylcarbodiimide

DIPEA:

N,N-diisopropylethylamine

DhBTOH:

3-hydroxy-1,2,3-benzotriazin-4(3H)-one

DMF:

N,N-dimethylformamide

EDC:

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

HBTU:

O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

HOBt:

1-hydroxy-1,2,3-benzotriazole

MBHA:

4-methyl benzhydrylamine

NMP:

N-methylpyrrolidone

TFA:

Trifluoroacetic acid

TFMSA:

Trifluoromethanesulfonic acid

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Acknowledgments

This work was supported by the Italian Ministry of University and Research (MIUR) with the national projects PRIN 2007 and PRIN 2009.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Parma, Parma, Italy

    Roberto Corradini & Rosangela Marchelli

  2. Department of Food Science, University of Parma, Parma, Italy

    Tullia Tedeschi & Stefano Sforza

Authors
  1. Roberto Corradini
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  2. Tullia Tedeschi
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  3. Stefano Sforza
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  4. Rosangela Marchelli
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Editor information

Editors and Affiliations

  1. Dept. Cellular & Molecular Medicine, University of Copenhagen Faculty of Health Sciences, Copenhagen N, Denmark

    Peter E Nielsen

  2. NIH NIDDK, Bethesda, USA

    Daniel H. Appella

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Corradini, R., Tedeschi, T., Sforza, S., Marchelli, R. (2014). Chiral PNAs with Constrained Open-Chain Backbones. In: Nielsen, P., Appella, D. (eds) Peptide Nucleic Acids. Methods in Molecular Biology, vol 1050. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-553-8_3

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  • DOI: https://doi.org/10.1007/978-1-62703-553-8_3

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-552-1

  • Online ISBN: 978-1-62703-553-8

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