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Solid-phase peptide synthesis (SPPS), C-terminal vs. side-chain anchoring: a reality or a myth

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Abstract

Here we review the strategies for the solid-phase synthesis of peptides starting from the side chain of the C-terminal amino acid. Furthermore, we provide experimental data to support that C-terminal and side-chain syntheses give similar results in terms of purity. However, the stability of the two bonds that anchor the peptide to the polymer may determine the overall yield and this should be considered for the large-scale production of peptides. In addition, resins/linkers which do not subject to side reactions can be preferred for some peptides.

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Acknowledgments

The work was partially supported by UKZN and NRF (South Africa) and CICYT (CTQ2012-30930), the Generalitat de Catalunya (2009SGR 1024), and the Institute for Research in Biomedicine (Spain).

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Authors declare that they do not have any financial conflict of interest.

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Authors and Affiliations

  1. Catalysis and Peptide Research Unit, School of Health Sciences, University of Kwazulu-Natal, Durban, 4001, South Africa

    Prabhakar Cherkupally, Suhas Ramesh, Beatriz G. De la Torre, Thavendran Govender, Hendrik G. Kruger & Fernando Albericio

  2. Institute for Research in Biomedicine (IRB Barcelona) Barcelona, Baldiri Reixac 10, 08028, Barcelona, Spain

    Prabhakar Cherkupally, Gerardo A. Acosta & Fernando Albericio

  3. CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, Baldiri Reixac 10, 08028, Barcelona, Spain

    Gerardo A. Acosta & Fernando Albericio

  4. Department of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003, Barcelona, Spain

    Beatriz G. De la Torre

  5. School of Chemistry and Physics, University of Kwazulu-Natal, Durban, 4001, South Africa

    Fernando Albericio

  6. Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028, Barcelona, Spain

    Fernando Albericio

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  1. Prabhakar Cherkupally
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  2. Gerardo A. Acosta
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  3. Suhas Ramesh
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  4. Beatriz G. De la Torre
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  5. Thavendran Govender
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  6. Hendrik G. Kruger
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  7. Fernando Albericio
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Correspondence to Fernando Albericio.

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Cherkupally, P., Acosta, G.A., Ramesh, S. et al. Solid-phase peptide synthesis (SPPS), C-terminal vs. side-chain anchoring: a reality or a myth. Amino Acids 46, 1827–1838 (2014). https://doi.org/10.1007/s00726-014-1746-7

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