Skip to main content
SpringerLink
Log in

Microwave-Assisted Solid-Phase Peptide Synthesis Based on the Fmoc Protecting Group Strategy (CEM)

  • Protocol
  • First Online:
Peptide Synthesis and Applications

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1047))

Abstract

Microwave-assisted peptide synthesis has become one of the most widely used tools by peptide chemists for the synthesis of both routine and difficult peptide sequences. Microwave technology significantly reduces the synthesis time while also improving the quality of the peptides produced. Microwave energy allows most amino acid couplings to be completed in just 5 min. The Fmoc removal can also be accelerated in the microwave decreasing the reaction time from at least 15 min to only 3 min in most cases. Common side reactions such as racemization and aspartimide formation are easily controllable with optimized methods that can be applied routinely. This protocol outlines the detailed procedure for performing both manual and automated microwave-assisted peptide synthesis of two difficult peptide sequences, ACP (65–74) and β-amyloid, in high purity and yield.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Merrifield RB (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85:2149–2154

    Article  CAS  Google Scholar 

  2. Lew A, Krutzik PO, Hart ME, Chamberlin AR (2002) Increasing rates of reaction: microwave-assisted organic synthesis for combinatorial chemistry. J Comb Chem 4:95–105

    Article  PubMed  CAS  Google Scholar 

  3. Loupy A (ed) (2006) Microwaves in organic synthesis. Wiley-VCH, Weinheim

    Google Scholar 

  4. Hayes BL (2002) Microwave synthesis: chemistry at the speed of light. CEM, Matthews

    Google Scholar 

  5. Loupy A (ed) (2002) Microwaves in organic synthesis. Wiley-VCH, Weinheim

    Google Scholar 

  6. Kappe CO, Stadler A (2005) Microwaves in organic and medicinal chemistry. Wiley-VCH, Weinheim

    Book  Google Scholar 

  7. Lidström P, Tierney JP (eds) (2005) Microwave-assisted organic synthesis. Blackwell, Oxford

    Google Scholar 

  8. Kappe CO, Dallinger D, Murphee SS (2009) Practical microwave synthesis for organic chemists: strategies, instruments, and protocols. Wiley-VCH, Weinheim

    Google Scholar 

  9. Leadbeater NE (ed) (2010) Microwave heating as a tool for sustainable chemistry. CRC Press, Boca Raton

    Google Scholar 

  10. Yu HM, Chen ST, Wang KT (1992) Enhanced coupling efficiency in solid-phase peptide-synthesis by microwave irradiation. J Org Chem 57:4781–4784

    Article  CAS  Google Scholar 

  11. Palasek SA, Cox ZJ, Collins JM (2007) Limiting racemization and aspartimide formation in microwave-enhanced Fmoc solid phase peptide synthesis. J Pept Sci 13:143–148

    Article  PubMed  CAS  Google Scholar 

  12. Collins JM, Unpublished results

    Google Scholar 

  13. Collins JM (2006) Microwave-enhanced solid-phase peptide synthesis. In: Loupy A (ed) Microwaves in organic synthesis. Wiley-VCH, Weinheim

    Google Scholar 

  14. Vanier GS (2010) Microwave heating as a tool for the biosciences. In: Leadbeater NE (ed) Microwave heating as a tool for sustainable chemistry. CRC Press, Boca Raton, pp 231–269

    Google Scholar 

  15. Pedersen SL, Tofteng AP, Malik L, Jensen KJ (2012) Microwave heating in solid-phase peptide synthesis. Chem Soc Rev 41:1826–1844

    Article  PubMed  CAS  Google Scholar 

  16. Collins JM, Leadbeater NE (2007) Microwave energy: a versatile tool for the biosciences. Org Biomol Chem 5:1141–1150

    Article  PubMed  CAS  Google Scholar 

  17. Hossain MA, Rosengren KJ, Haugaard-Jonsson LM, Zhang S, Layfield S, Ferraro T, Daly NL, Tregear GW, Wade JD, Bathgate RAD (2008) The A-chain of human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors. J Biol Chem 283:17287–17297

    Article  PubMed  CAS  Google Scholar 

  18. Hossain MA, Rosengren KJ, Zhang S, Bathgate RA, Tregear GW, van Lierop BJ, Robinson AJ, Wade JD (2009) Solid phase synthesis and structural analysis of novel A-chain dicarba analogs of human relaxin-3 (INSL7) that exhibit full biological activity. Org Biomol Chem 7:1547–1553

    Article  PubMed  CAS  Google Scholar 

  19. Grummitt CG, Townsley FM, Johnson CM, Warren AJ, Bycroft M (2008) Structural consequences of nucleophosmin mutations in acute myeloid leukemia. J Biol Chem 283:23326–23332

    Article  PubMed  CAS  Google Scholar 

  20. Drew SC, Masters CL, Barnham KJ (2009) Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer’s disease amyloid-beta peptide—relevance to N-terminally truncated forms. J Am Chem Soc 131:8760–8761

    Article  PubMed  CAS  Google Scholar 

  21. Drew SC, Noble CJ, Masters CL, Hanson GR, Barnham KJ (2009) Pleomorphic copper coordination by Alzheimer’s disease amyloid-beta peptide. J Am Chem Soc 131:1195–1207

    Article  PubMed  CAS  Google Scholar 

  22. Mosse WK, Koppens ML, Gengenbach TR, Scanlon DB, Gras SL, Ducker WA (2009) Peptides grafted from solids for the control of interfacial properties. Langmuir 25:1488–1494

    Article  PubMed  CAS  Google Scholar 

  23. Harterich S, Koschatzky S, Einsiedel J, Gmeiner P (2008) Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1, ligand backbone methylations and molecular modeling of neurotensin receptor 1. Bioorg Med Chem 16:9359–9368

    Article  PubMed  Google Scholar 

  24. Grieco P, Cai M, Liu L, Mayorov A, Chandler K, Trivedi D, Lin G, Campiglia P, Novellino E, Hruby VJ (2008) Design and microwave-assisted synthesis of novel macrocyclic peptides active at melanocortin receptors: discovery of potent and selective hMC5R receptor antagonists. J Med Chem 51:2701–2707

    Article  PubMed  CAS  Google Scholar 

  25. Bin Zhang H, Chi YS, Huang WL, Ni SJ (2007) Total synthesis of human urotension-II by microwave-assisted solid phase method. Chin Chem Lett 18:902–904

    Article  Google Scholar 

  26. Tofteng AP, Jensen KJ, Schaffer L, Hoeg-Jensen T (2008) Total synthesis of desB30 insulin analogues by biomimetic folding of single-chain precursors. Chembiochem 9:2989–2996

    Article  PubMed  CAS  Google Scholar 

  27. Schäffer L, Brand CL, Hansen BF, Ribel U, Shaw AC, Slaaby R, Sturis J (2008) A novel high-affinity peptide antagonist to the insulin receptor. Biochem Biophys Res Commun 376:380–383

    Article  PubMed  Google Scholar 

  28. Shabanpoor F, Hughes RA, Bathgate RA, Zhang S, Scanlon DB, Lin F, Hossain MA, Separovic F, Wade JD (2008) Solid-phase synthesis of europium-labeled human INSL3 as a novel probe for the study of ligand-receptor interactions. Bioconjug Chem 19:1456–1463

    Article  PubMed  CAS  Google Scholar 

  29. Armishaw C, Jensen AA, Balle T, Clark RJ, Harpsoe K, Skonberg C, Liljefors T, Stromgaard K (2009) Rational design of alpha-conotoxin analogues targeting alpha7 nicotinic acetylcholine receptors: improved antagonistic activity by incorporation of proline derivatives. J Biol Chem 284:9498–9512

    Article  PubMed  CAS  Google Scholar 

  30. Cassone M, Vogiatzi P, La Montagna R, De Olivier Inacio V, Cudic P, Wade JD, Otvos L Jr (2008) Scope and limitations of the designer proline-rich antibacterial peptide dimer, A3-APO, alone or in synergy with conventional antibiotics. Peptides 29:1878–1886

    Article  PubMed  CAS  Google Scholar 

  31. Noto PB, Abbadessa G, Cassone M, Mateo GD, Agelan A, Wade JD, Szabo D, Kocsis B, Nagy K, Rozgonyi F, Otvos L Jr (2008) Alternative stabilities of a proline-rich antibacterial peptide in vitro and in vivo. Protein Sci 17:1249–1255

    Article  PubMed  CAS  Google Scholar 

  32. James PF, Dogovski C, Dobson RCJ, Bailey MF, Goldie KN, Karas JA, Scanlon DB, O'Hair RAJ, Perugini MA (2009) Aromatic residues in the C-terminal helix of human apoC-I mediate phospholipid interactions and particle morphology. J Lipid Res 50:1384–1394

    Article  PubMed  CAS  Google Scholar 

  33. Chi Y, Zhang H, Huang W, Zhou J, Zhou Y, Qian H, Ni S (2008) Microwave-assisted solid phase synthesis, PEGylation, and biological activity studies of glucagon-like peptide-1(7-36) amide. Bioorg Med Chem 16:7607–7614

    Article  PubMed  CAS  Google Scholar 

  34. Murray JK, Aral J, Miranda LP (2011) Solid-phase peptide synthesis using microwave irradiation. In: Satyanarayanajois SD (ed) Drug design and discovery: methods and protocols. Springer Science+Business Media, LLC, New York

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CEM Corporation, Matthews, NC, USA

    Grace S. Vanier

Authors
  1. Grace S. Vanier
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. IGM, Faculty of Sciences, University of Copenhagen, Frederiksberg, Denmark

    Knud J. Jensen

  2. IGM, Faculty of Science, University of Copenhagen, Glostrup, Denmark

    Pernille Tofteng Shelton

  3. IGM, Faculty of Life Sciences, University of Copenhagen, Hørsholm, Denmark

    Søren L. Pedersen

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media, New York

About this protocol

Cite this protocol

Vanier, G.S. (2013). Microwave-Assisted Solid-Phase Peptide Synthesis Based on the Fmoc Protecting Group Strategy (CEM). In: Jensen, K., Tofteng Shelton, P., Pedersen, S. (eds) Peptide Synthesis and Applications. Methods in Molecular Biology, vol 1047. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-544-6_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-544-6_17

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-543-9

  • Online ISBN: 978-1-62703-544-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation