Introducing an Asp-Pro Linker in the Synthesis of Random One-Bead-One-Compound Hexapeptide Libraries Compatible with ESI-MS Analysis

peer-reviewed · ACS Combinatorial Science · 2012

peer-reviewed · ACS Combinatorial Science · 2012. Yordanka Masforrol et al. A random hexapeptide library (one-bead-one-compound), containing sixteen amino acids (16(6) different…
Date 2012-03-12
Type peer-reviewed
Venue ACS Combinatorial Science
Publisher American Chemical Society (ACS)
Contribution adjacent
DOI 10.1021/co200159r
Citations (OpenAlex) 8

Abstract

A random hexapeptide library (one-bead-one-compound), containing sixteen amino acids (16(6) different sequences) was synthesized on a Tentagel resin previously modified with a dipeptide linker (Asp-Pro). This peptide bond is highly susceptible to cleavage under mild acidic conditions in a salt-free solution prepared with H(2)(16)O/H(2)(18)O (60/40% v/v). In the hydrolysis, hexapeptides are released with an additional Asp residue partially labeled with (18)O at the C-terminus. These conditions are fully compatible with ESI-MS analysis and facilitate sequencing by MS, as N- and C-terminal ions can be easily differentiated in MS/MS spectra. The peptides were sequenced manually and also with de novo sequencing programs, and identifying them in a database containing all possible heptapeptide sequences or in a filtered database. The proposed strategy is also compatible with stepwise Edman degradation using either intact beads or the released free peptides.

Authors

  1. Yordanka Masforrol · Centro de Ingeniería Genética y Biotecnología
  2. Jeovanis Gil · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Centro de Ingeniería Genética y Biotecnología, Institute for Research in Biomedicine, Karolinska Institutet, Parc Científic de Barcelona, Universitat de Barcelona
  3. Luis Javier González · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Center for Genetic Engineering and Biotechnology, Centro de Ingeniería Genética y Biotecnología, Institute for Research in Biomedicine, Karolinska Institutet, Parc Científic de Barcelona, Universitat de Barcelona
  4. Yasset Perez-Riverol · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Centro de Ingeniería Genética y Biotecnología, European Molecular Biology Laboratory, Institute for Research in Biomedicine, Karolinska Institutet, Parc Científic de Barcelona, Universitat de Barcelona
  5. Jorge Fernández-de-Cossío · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Center for Genetic Engineering and Biotechnology, Centro de Ingeniería Genética y Biotecnología, Institute for Research in Biomedicine, Karolinska Institutet, Osaka University, Parc Científic de Barcelona, Universitat de Barcelona
  6. Aniel Sánchez · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Centro de Ingeniería Genética y Biotecnología, Institute for Research in Biomedicine, Karolinska Institutet, Parc Científic de Barcelona, Universitat de Barcelona
  7. Lázaro Betancourt · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Center for Genetic Engineering and Biotechnology, Centro de Ingeniería Genética y Biotecnología, Institute for Research in Biomedicine, Karolinska Institutet, Parc Científic de Barcelona, Universitat de Barcelona
  8. Hilda Elisa Garay · Centro de Ingeniería Genética y Biotecnología
  9. Ania Cabrales · Centro de Ingeniería Genética y Biotecnología
  10. Fernando Albericio · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Institute for Research in Biomedicine, Parc Científic de Barcelona, Universitat de Barcelona
  11. Hongqian Yang · Karolinska Institutet
  12. Roman A. Zubarev · Cornell University, Karolinska Institutet, Uppsala University
  13. Vladimir Besada · Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Center for Genetic Engineering and Biotechnology, Centro de Ingeniería Genética y Biotecnología, Institute for Research in Biomedicine, Karolinska Institutet, Parc Científic de Barcelona, Universitat de Barcelona
  14. Osvaldo Reyes Acosta · Centro de Ingeniería Genética y Biotecnología

Methods and tools

  • Asp-Pro linker 18O OBOC peptide sequencing: Releases one-bead-one-compound hexapeptides through an acid-labile Asp-Pro linker in partly 18O water, so N- and C-terminal ions can be told apart during de novo sequencing.

Methods it uses

  • PEAKS: Commercial DP-based de novo

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