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Synthesis of Amide Backbone-Modified Peptides

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Book cover Peptide Synthesis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2103))

Abstract

Solubility is a key property of peptides and of central importance to the success of solid-phase peptide synthesis and subsequent peptide purification and handling. Substitution of the backbone amide bond can dramatically increase peptide solubility. Backbone amide bond protection works by preventing the formation of interchain association and can be used both to synthesize aggregation-prone peptide sequences on solid phase and to improve solubility of a peptide post synthesis. Improving peptide solubility by judicial use of backbone protection is of growing importance, particularly for chemical protein synthesis by chemical ligation.

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Abbreviations

Aa:

amino acid

ACN:

acetonitrile

CHCA:

α-cyano-4-hydroxycinnamic acid

DCM:

dichloromethane

DIC:

1,3-diisopropylcarbodiimide

DIEA:

N,N-diisopropylethylamine

DMF:

N,N-dimethylformamide

DMSO:

dimethyl sulfoxide

EDT:

1,2-ethanedithiol

Fmoc:

9-fluorenylmethoxycarbonyl

HCTU:

O-(6-chlorobenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate

Hmb:

2-hydroxy-4-methoxybenzyl

Hmsb:

2-hydroxy-4-methoxy-5-methylsulfinyl benzyl

HOBt:

1-hydroxybenzotriazole

MALDI-MS:

matrix-assisted laser desorption ionization mass spectrometry

MW:

microwave

NMP:

N-methyl-2-pyrrolidone

TES:

triethylsilane

TFA:

trifluoroacetic acid

TMSBr:

trimethylsilyl bromide

TNBS:

2,4,6-trinitrobenzene sulfonic acid

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Authors and Affiliations

  1. The Francis Crick Institute, London, UK

    Abu-Baker M. Abdel-Aal, Richard Raz, George Papageorgiou & John Offer

Authors
  1. Abu-Baker M. Abdel-Aal
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  2. Richard Raz
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  3. George Papageorgiou
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  4. John Offer
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Corresponding author

Correspondence to John Offer .

Editor information

Editors and Affiliations

  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia

    Waleed M. Hussein

  2. School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia

    Mariusz Skwarczynski

  3. School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia

    Istvan Toth

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Abdel-Aal, AB.M., Raz, R., Papageorgiou, G., Offer, J. (2020). Synthesis of Amide Backbone-Modified Peptides. In: Hussein, W., Skwarczynski, M., Toth, I. (eds) Peptide Synthesis. Methods in Molecular Biology, vol 2103. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0227-0_15

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  • DOI: https://doi.org/10.1007/978-1-0716-0227-0_15

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0226-3

  • Online ISBN: 978-1-0716-0227-0

  • eBook Packages: Springer Protocols

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