Skip to main content
SpringerLink
Log in

Depsipeptide Synthesis

  • Protocol
Book cover Peptide Characterization and Application Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 386))

Summary

Naturally occurring cyclic depsipeptides, peptides that contain one or more ester bonds in addition to the amide bonds, have emerged as an important source of pharmacologically active compounds or promising lead structures for the development of novel synthetically derived drugs. This class of natural products has been found in many organisms, such as fungi, bacteria, and marine organisms. It is very well known that cyclic depsipeptides and their derivatives exhibit a diverse spectrum of biological activities, including insecticidal, antiviral, antimicrobial, antitumor, tumor-promotive, anti-inflammatory, and immunosuppressive actions. However, they have shown the greatest therapeutic potential as anticancer and particularly antimicrobial agents. Difficulties associated with isolation and purification of larger quantities of this class of natural products and, particularly, unlimited access to their synthetic analogs significantly hampered cyclic depsipeptides exploitation as lead compounds for development of new drugs. As an alternative, total solution or solid-phase peptide synthesis of these important natural products and combinatorial chemistry approaches can be employed to elucidate structure–activity relationships and to find new potent compounds of this class. In this chapter, methods for formation of depsipeptide ester bonds, hydroxyl group protection, and solid-phase reaction monitoring are described.

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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. Grabley, S. and Thiericke, R., (1999) Drug Discovery from Nature. Springer-Verlag, Heidelberg.

    Google Scholar 

  2. Newman, D. J., Cragg, G. M., and Snader K. M. (2003) Natural products as sources of new drugs over the period 1981–2002. J. Nat. Prod. 66, 1022–1037.

    Article  PubMed  CAS  Google Scholar 

  3. Cragg, G. M., Newman, D. J., and Snader, K. M. (1997) Natural products in drug discovery development. J. Nat. Prod. 60, 52–60.

    Article  PubMed  CAS  Google Scholar 

  4. Bozdogan, B., Esel, D., Whitener, C., Browne, F. A., and Appelbaum P. C. (2003) Antibacterial susceptibility of a vancomycin-resistant Staphylococcus aureus strain isolated at the Hershey Medical Center. J. Antimicrob. Chemother. 52, 864–868.

    Article  PubMed  CAS  Google Scholar 

  5. Loffet A. (2002) Peptides as drugs: is there a market? J. Pept. Sci. 8, 1–7.

    Article  PubMed  CAS  Google Scholar 

  6. Loffet A. (2001) Peptides as drugs: is there a market? Peptides: The Wave of the Future ( Lebl, M. and Hougten, R. A., eds.). American Peptide Society: pp. 214–216.

    Google Scholar 

  7. Andersson, L., Blomberg, L., Flegl, M., Lepsa, L., Nilsson, B., and Verlander M. (2000) Large-scale synthesis of peptides. Biopolymers 55, 227–250.

    Article  PubMed  CAS  Google Scholar 

  8. Verlander M. (2000) Large-scale manufacturing methods for peptides—a status report. Chim. Oggi, 20, 62–66.

    Google Scholar 

  9. Adessi, C. and Soto, C. (2002) Converting a peptide into drug: strategies to improve stability and bioavailability. Curr. Med. Chem. 9, 963–978.

    Article  PubMed  CAS  Google Scholar 

  10. Davies, J. S. (2003) The cyclization of peptides and depsipeptides. J. Pept. Sci. 9, 471–501.

    Article  PubMed  CAS  Google Scholar 

  11. Lambert, J. N., Mitchell, J. P., and Roberts, K. D. (2001) The synthesis of cyclic peptides. J. Chem. Soc, Perkin Trans. 1, 471–484.

    Article  Google Scholar 

  12. Li, P. and Roller, P. P. (2002) Cyclization strategies in peptide derived drug design. Curr. Top. Med. Chem. 2, 325–341.

    Article  PubMed  CAS  Google Scholar 

  13. Blackburn, C. and Kates, S. A. (1997) Solid-phase synthesis of cyclic homodetic peptides. Methods Enzymol. 289, 175–198.

    Article  PubMed  CAS  Google Scholar 

  14. Hruby, V. J. and Bonner, G. G. (1994) Design of novel synthetic peptides including cyclic conformationally and topographically constrained analogs. Methods. Mol. Biol. 35, 201–240.

    PubMed  CAS  Google Scholar 

  15. Kates, S. A., Sole, N. A., Albericio, F., and Barany, G. (1994) Solid-phase synthesis of cyclic peptides, in Peptides: Design, Synthesis, and Biological Activity. Brikhauser Boston: pp. 39–59.

    Google Scholar 

  16. Shemyakin, M. M., Shchukina, L. A., Vinogradova, E. I., Ravidel, G. A., and Ovchinnikov, Y. A. (1966) Mutual replaceability of amide and ester groups in biologically active peptide and depsipeptides. Experimentia 22, 535–536.

    Article  CAS  Google Scholar 

  17. Bramson, H. N., Thomas, N. E., and Kaiser, E. T. (1985) The use of N-methylated peptides and depsipeptides to probe the binding of heptapeptide substrates to cAMP-dependent protein kinase. J. Biol. Chem. 260, 15,452–15,457.

    CAS  Google Scholar 

  18. Arad, O. and Goodman, M., (1990) Depsipeptide analogues of elastin repeating sequences: synthesis. Biopolymers, 29, 1633–1649.

    Article  PubMed  CAS  Google Scholar 

  19. Coombs, G. S., Rao, M. S., Olson, A. J., Dawson, P. E., and Madison, E. L. (1999) Revisiting catalysis by chymotrypsin family serine proteases using peptide substrates and inhibitors with unnatural main chains. J. Biol. Chem. 274, 24,074–24,079.

    Article  CAS  Google Scholar 

  20. Davidson, B. S. (1993) Ascidians: producers of amino acid-derived metabolites. Chem. Rev. 93, 1771–1791.

    Article  CAS  Google Scholar 

  21. Fusetani, N. and Matsunaga, S. (1993) Bioactive sponge peptides. Chem. Rev. 93, 1793–1806.

    Article  CAS  Google Scholar 

  22. Simmons, T. L., and rianasolo, E., McPhail, K., Flatt, P., and Gerwick, H. W. (2005) Marine natural products as anticancer drugs. Mol. Chem. Ther. 4, 333–342.

    CAS  Google Scholar 

  23. Woodford, N. (2003) Novel agents for the treatment of resistant Gram-positive infections. Expert. Opin. Investig. Drugs. 12, 117–137.

    Article  PubMed  CAS  Google Scholar 

  24. McCafferty, D. G., Cudic, P., Frankel, B. A., Barkallah, S., Kruger, R. G., and Li, W. (2002) Chemistry and biology of the ramoplanin family of peptide antibiotics. Biopolymers 66, 261–284.

    Article  PubMed  CAS  Google Scholar 

  25. Humphrey, J. M. and Chamberlin, A. R. (1997) Chemical synthesis of natural product peptides: coupling methods for the incorporation of noncoded amino acids into peptides. Chem. Rev. 97, 2243–2266.

    Article  PubMed  CAS  Google Scholar 

  26. Anteunis, M. O. J. and Sharma, N. K. (1988) N,N′-Bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl) mediated cyclization of a linear precursor of virginiamycin S. Contra indication for using hydroxybenzotriazole as racemization suppressor. Bull. Soc. Chim. Belg. 97, 281–292.

    Article  CAS  Google Scholar 

  27. Kopple, K. D. (1972) Synthesis of cyclic peptides. J. Pharm. Sci. 61, 1345–1356.

    Article  CAS  Google Scholar 

  28. Brady, S. F., Varga, S. L., Freidinger, R. M., et al. (1979) Practical synthesis of cyclic peptides, with an example of dependence of cyclization yield upon linear sequence. J. Org. Chem. 44, 3101–3105.

    Article  CAS  Google Scholar 

  29. Chu, K. S., Negrete, G. R., and Konopelski, J. P. (1991) Asymmetric total synthesis of (+) jasplakinolide. J. Org. Chem. 56, 5196–5202.

    Article  CAS  Google Scholar 

  30. White, J. D. and Amedio, J. C. (1989) Total synthesis of geodiamolide A—a novel cyclodepsipeptide of marine origin. J. Org Chem. 54, 736–738.

    Article  CAS  Google Scholar 

  31. Marder, O. and Albericio, F. (2003) Industrial application of coupling reagents in peptides. Chim. Oggi 6, 35–40.

    Google Scholar 

  32. Berry J. D., Digiovanna V. C., Metrick S. S., and Murugan R. (2001) Catalysis by 4-Dialkylaminopyridines. Arkivoc i, 201–226

    Google Scholar 

  33. Kuisle, O., Lolo, M., Quinoa, E., and Riguera, R., (1999) Solid Phase Synthesis of Depsides and Depsipeptides. Tetrahedron 55, 14,807–14,812.

    Article  CAS  Google Scholar 

  34. Kuisle, O., Quinoa, E., and Riguera, R., (1999) A general methodology for automated solid-phase synthesis of depsides and depsipeptides. Preparation of a valinomycin analogue. J. Org Chem. 64, 8063–8075.

    Article  PubMed  CAS  Google Scholar 

  35. Stawikowski, M. and Cudic, P. (2006) A novel strategy for the solid-phase synthesis of cyclic lipodepsipeptides. Tetrahedron Lett. 47, 8587–8590.

    Article  PubMed  CAS  Google Scholar 

  36. Murakami, N., Wang, W., Tamura, S., and Kobayashi, M. (2000) Synthesis and biological property of carba and 20-deoxo analogues of arenastatin A. Bioorg Med. Chem. Lett. 10, 1823–18236.

    Article  PubMed  CAS  Google Scholar 

  37. Joullie, M. M., Portonovo, P., Liang, B., and Richard, D. J. (2000) Total synthesis of (–)-tamandarin B. Tetrahedron Lett. 41, 9373–9376.

    Article  CAS  Google Scholar 

  38. Dutton, F. E., Byung, H. L., Johnson, S. S. Coscarelli, E.M., and Lee P. H. (2003) Restricted conformation analogues of anthelmintic cyclopeptide. J. Med. Chem., 46, 2057–2073.

    Article  PubMed  CAS  Google Scholar 

  39. Katakai, R., Kobayashi, K., Yamada, K., Oku, H., and Emori, N. (2004) Synthesis of sequential polydepsipeptides utilizing a new approach for the synthesis of depsipeptides. Biopolymers 73, 641–644.

    Article  PubMed  CAS  Google Scholar 

  40. Mitsunobu, O. and Yamada, M. (1967) Preparation of esters of carboxylic and phosphoric acid via quaternary phosphonium salts. Bull.Chem. Soc. Jpn. 40, 2380–2382

    Article  CAS  Google Scholar 

  41. Mitsunobu, O. (1981) The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products. Synthesis 1, 1–28.

    Article  Google Scholar 

  42. Boger, D. L., Keim, H., Oberhauser, B., Schreiner, E. P., and Foster, C. A. (1999) Total synthesis of HUN-7293. J. Am. Chem. Soc. 121, 6197–6205

    Article  CAS  Google Scholar 

  43. Grab, T. and Brase S. (2005) Efficient synthesis of lactate-containing depsipeptides by the Mitsunobu reaction of lactates. Adv. Synth. Catal. 347, 1765–1768.

    Article  CAS  Google Scholar 

  44. Inanaga, J., Hirata, K., Saeki, H., Katsuki, T., and Yamaguchi, M. (1979) Rapid esterification by means of mixed anhydride and its application to large-ring lactonization. Bull. Chem. Soc. Jpn. 52, 7, 1989–1993.

    Article  CAS  Google Scholar 

  45. Chen, J. and Forsyth, J. C. (2004) Natural product synthesis special feature: total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A. Proc. Natl. Acad. Sci. USA 101, 12,067–12,072.

    CAS  Google Scholar 

  46. Zou, B., Long, K, and Ma, D. (2005) Total synthesis and cytotoxicity studies of a cyclic depsipeptide with proposed structure of palau’amide. Org. Lett. 7, 4237–4240.

    Article  PubMed  CAS  Google Scholar 

  47. Davies, J. S., Howe, J., Jayatilake J., and Riley T. (1997) Synthesis and applications of cyclopeptides and depsipeptides. Lett. Pept. Sci. 4, 441–445.

    CAS  Google Scholar 

  48. Albericio, F., Burger, K, Ruiz-Rodrigez, J., and Spengler, J. (2005) A new strategy for solid-phase depsipeptide synthesis using recoverable building blocks. Org. Lett. 7, 597–600.

    Article  PubMed  CAS  Google Scholar 

  49. Albericio, F., Burger, K., Cupido, T. K, Ruiz, J., and Spengler, J. (2005) Application of hexafluoroacetone as protecting and activating reagent in solid phase peptide and depsipeptide synthesis. Arkivoc vi, 191–199.

    Google Scholar 

  50. Corey, E. J., Cho, H., Rucker, C., and Hua, D., H. (1981) Studies with trialkylsilyltriflates: new syntheses and applications. Tetrahedron Lett. 22, 3455–3458.

    Article  CAS  Google Scholar 

  51. Yuan, W., Jia, Y., Tian, J., et al. (2001) Class I and III polyhydroxyalkanoate synthases from Ralstonia eutopha and Allochromatium vinosum: characterization and substrate specificity studies. Arch. Biochem. Biophys. 394, 87–98.

    Article  PubMed  CAS  Google Scholar 

  52. Burger, K., Windeisen, E., and Pires, R., (1995) New efficient strategy for the incorporation of (S)-isoserine into peptides. J. Org. Chem. 60, 7641–7645.

    Article  CAS  Google Scholar 

  53. Radics, G., Pires, R., Koksch, B., El-Kousy, S. M., and Burger, K. (2003) New building blocks for peptide and depsipeptide synthesis: hexafluoroacetone protected L-homoserine and D,L-homocysteine derivatives. Tetrahedron Lett. 44, 1059–1062.

    Article  CAS  Google Scholar 

  54. Kaiser, E., Colescott, R. L., Bossinger, C. D., and Cook, P. I. (1970) Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal. Biochem. 34, 595–598.

    Article  PubMed  CAS  Google Scholar 

  55. Pomonis, J. G., Severson, R. F., and Freeman, P. J. (1969) Spot test diagnostic of hydroxyl groups. J. Chromatog. 40, 78–84.

    Article  CAS  Google Scholar 

  56. Kuisle, O., Lolo, M., Quinoa, E., and Riguera, R., (1999) Monitoring the solid-phase synthesis of depsides and depsipeptides. A color test for hydroxyl groups linked to a resin. Tetrahedron 55, 14,807–14,812.

    Article  CAS  Google Scholar 

  57. Attardi, M. E., Falchi, A., and Taddei, M. (2000) A sensitive visual test for detection of OH groups on resin. Tetrahedron Lett. 41, 7395–7399.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry & Biochemistry, Florida Atlantic University, Boca Raton, FL

    Maciej Stawikowski & Predrag Cudic

Authors
  1. Maciej Stawikowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Predrag Cudic
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL

    Gregg B. Fields

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc.

About this protocol

Cite this protocol

Stawikowski, M., Cudic, P. (2007). Depsipeptide Synthesis. In: Fields, G.B. (eds) Peptide Characterization and Application Protocols. Methods in Molecular Biology™, vol 386. Humana Press. https://doi.org/10.1007/978-1-59745-430-8_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-430-8_13

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-550-7

  • Online ISBN: 978-1-59745-430-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation