Skip to main content

Using a Noncovalent Protection Strategy to Enhance Solid-Phase Synthesis

  • Protocol
Combinatorial Library

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 201))

  • 509 Accesses

Abstract

Since the introduction of solid-phase peptide synthesis by Merrifield (1) nearly forty years ago, solid-phase techniques have been applied to the construction of a variety of biopolymers and extended into the field of small molecule synthesis. The last decade has seen the emergence of solid-phase synthesis as the leading technique in the development and production of combinatorial libraries of diverse compounds of varying sizes and properties. Combinatorial libraries can be classified as biopolymer based (e.g., peptides, peptidomimetics, polyureas, and others [2,3]) or small molecule based (e.g., heterocycles [4], natural product derivatives [5], and inorganic complexes [6,7]). Libraries synthesized by solid-phase techniques mainly use polystyrene-divinylbenzene (PS) derived solid supports. Owing to physical and chemical limitations of PS-derived resins, other resins have been developed (8,9). Most of these resins are prepared from PS by functionalizing the resin beads with oligomers to improve solvent compatibility and physical stability (8,9).

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

Access this chapter

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 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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 R. B. (1963) Solid-phase peptide synthesis I. J. Am. Chem. Soc. 85, 2149–2154.

    Article  CAS  Google Scholar 

  2. Al-Obeidi F. A., Hruby V. J., and Sawyer T. K. (1998) Peptide and pepti-domimetic libraries. Mol. Biotech. 9, 205–223.

    Article  CAS  Google Scholar 

  3. Dolle R. E. (2000) Comprehensive survey of combinatorial library synthesis: 1999. J. Combi. Chem. 2, 384–433.

    Google Scholar 

  4. Franzen R. G. (2000) Recent advances in the preparation of heterocycles on solid support: a review of the literature. J. Comb. Chem. 2, 195–214.

    Article  PubMed  CAS  Google Scholar 

  5. Hall D. G., Manku S., and Wang F. (2001) Solution-and solid-phase strategies for the design, synthesis, and screening of libraries based on natural product templates: a comprehensive survey. J. Comb. Chem. 3, 125–150.

    Article  PubMed  CAS  Google Scholar 

  6. Schultz P. G. and Xiang X.-D. (1998) Combinatorial approaches to materials science. Curr. Opin. Solid State Mater. Sci. 3, 153–158.

    Article  CAS  Google Scholar 

  7. Gennari F., Seneci P., and Miertus S. (2000) Application of combinatorial technologies for catalyst design and development. Catal. Rev. Sci. Eng. 42, 385–402.

    Article  CAS  Google Scholar 

  8. Hudson D. (1999) Matrix assisted synthetic transformations: a mosaic of diverse contributions. I. The pattern emerges. J. Comb. Chem. 1, 333–360.

    Article  PubMed  CAS  Google Scholar 

  9. Hudson D. (1999) Matrix assisted synthetic transformations: a mosaic of diverse contributions. II. The pattern emerges. J. Comb. Chem. 1, 404–457.

    Google Scholar 

  10. Eggenweiler H.-M. (1998) Linkers for solid-phase synthesis of small molecules: coupling and cleavage techniques. Drug Discov. Today 3, 552–560.

    Article  CAS  Google Scholar 

  11. Dueholm K. L., Egholm M., Behrens C., Christensen L., Hansen H. F., Vulpius T., et al. (1994) Synthesis of peptide nucleic acid monomers containing the four natural nucleobases: thymine, cytosine, adenine and guanine and their oligomer-ization. J. Org. Chem. 59, 5767–5773.

    Article  CAS  Google Scholar 

  12. Thomson S. A., Josey J. A., Cadilla R., Gaul M., Hassman C. F., Luzzio M. J., et al. (1995) Fmoc mediated synthesis of peptide nucleic acids. Tetrahedron 51, 6179–6194.

    Article  CAS  Google Scholar 

  13. Hyde C. B., Welham K. J., and Mascagni P. (1989) The use of crown ethers in peptide chemistry. Part 2. Syntheses of dipeptide complexes with cyclic polyether 18-crown-6 and their derivatization with DMSO. J. Chem. Soc., Perkin Trans. 2 12, 2011–2015.

    Article  Google Scholar 

  14. Hyde C. B. and Mascagni P. (1990) The use of crown ethers in peptide chemis-try. Part 3. Synthesis of an enkephalin derivative using 18-crown-6 as a non-covalent amino protecting group. Tetrahedr. Lett. 31, 399–402.

    Article  CAS  Google Scholar 

  15. Botti P., Lucietto P., Pinori M., and Mascagni P. (1993) The use of crown-ethers as non-covalent protecting groups for the synthesis of peptides, in Innova-tion Perspectives on Solid Phase Synthesis, Collected Papers, 3rd International Symposium (1994), meeting date 1993, pp. 459–462.

    Google Scholar 

  16. Botti P., Ball H. L., Rizzi E., Lucietto P., Pinori M., and Mascagni P. (1995) The use of crown ethers in peptide chemistry. IV. Solid phase synthesis of pep-tides using peptide fragments Na protected with 18-crown-6. Tetrahedr. Lett. 51, 5447–5458.

    CAS  Google Scholar 

  17. Botti P., Ball H. L., Lucietto P., Pinori M., Rizzi E., and Mascagni P. (1996) The use of crown ethers in peptide chemistry. V. Solid-phase synthesis of pep-tides by the fragment condensation approach using crown ethers as non-covalent protecting groups. J. Pept. Sci. 2, 371–380.

    Article  PubMed  CAS  Google Scholar 

  18. Barrett A. G. M. and Lana J. C. A. (1978) Selective acylation of amines using 18-crown-6. J. Chem. Soc. Chem. Commun., 471–472.

    Google Scholar 

  19. Ha Y. L. and Chakraborty A. K. (1992) Nature of the interactions of 18-crown-6 with ammonium cations: a computational study. J. Phys. Chem. 96, 6410–6417.

    Article  CAS  Google Scholar 

  20. Liou C. C. and Brodbelt J. S. (1992) Comparison of gas-phase proton and ammonium ion affinities of crown ethers and related acyclic analogs. J. Am. Chem. Soc. 114, 6761–6764.

    Article  CAS  Google Scholar 

  21. Hiraoka M. (1982)Crown Compounds: Their Characteristics and Applications

    Google Scholar 

  22. Mascagni P., Hyde C. B., Charalambous M. A., and Welham K. J. (1987) The use of crown ethers in peptide chemistry. Part 1. Syntheses of amino acid com-plexes with the cyclic polyether 18-crown-6 and their oligomerisation in dicylohexylcarbodi-imide-containing solutions. J. Chem. Soc. Perkin Trans. 2, 323–327.

    Google Scholar 

  23. Lansdorp P. M., Verwoerd N. P., van de Rijke F. M., Dragowska V., Little M. T., Dirks R. W., et al. (1996) Heterogeneity in telomere length of human chromosomes. Hum. Mol. Genet. 5, 685–691.

    Article  PubMed  CAS  Google Scholar 

  24. Hamilton S. E., Simmons C. G., Kathiriya I. S., and Corey D. R. (1999) Cellu-lar delivery of peptide nucleic acids and inhibition of human telomerase. Chem. Biol. 6, 343–351.

    Article  PubMed  CAS  Google Scholar 

  25. Mayfield L. D. and Corey D. R. (1999) Enhancing solid phase synthesis by a noncovalent protection strategy-efficient coupling of rhodamine to resin-bound peptide nucleic acids. Bioorg. Med. Chem. Lett. 9, 1419–1422.

    Article  PubMed  CAS  Google Scholar 

  26. Braasch D. A. and Corey D. R. (2001) Synthesis, analysis, purification, and intra-cellular delivery of peptide nucleic acids. Methods 23, 97–107.

    Article  PubMed  CAS  Google Scholar 

  27. Mayfield L. D. and Corey D. R. (1999) Automated synthesis of peptide nucleic acids and peptide nucleic acid-peptide conjugate. Analyt. Biochem. 268, 401–404.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Humana Press Inc.

About this protocol

Cite this protocol

Al-Obeidi, F., Okonya, J.F., Austin, R.E., Bond, D.R.S. (2002). Using a Noncovalent Protection Strategy to Enhance Solid-Phase Synthesis. In: English, L.B. (eds) Combinatorial Library. Methods in Molecular Biology™, vol 201. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-285-6:03

Download citation

  • DOI: https://doi.org/10.1385/1-59259-285-6:03

  • Publisher Name: Springer, Totowa, NJ

  • Print ISBN: 978-0-89603-980-3

  • Online ISBN: 978-1-59259-285-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics