Efficient Synthesis of Peptides with 4-Methylpiperidine as Fmoc Removal Reagent by Solid Phase Synthesis

Authors

  • Javier Eduardo García Castañeda Universidad Nacional de Colombia
  • Cristian Francisco Vergel Galeano Universidad Nacional de Colombia
  • Zuly Jenny Rivera Monroy Universidad Nacional de Colombia
  • Javier Eduardo Rosas Pérez Universidad Nacional de Colombia

DOI:

https://doi.org/10.29356/jmcs.v58i4.47

Keywords:

Synthetic Peptide, piperidine, 4-methylpiperidine, Fmoc removal reaction, Solid Phase Peptide Synthesis

Abstract

Solid phase peptide synthesis using the Fmoc/t-Bu strategy (SPPS-Fmoc/tBu) is the most widely used methodology for obtaining synthetic peptides. In this paper, we evaluate the viability of using 4-methylpiperidine as a reagent for deprotection of the amino acid alpha amino group in SPPS-Fmoc/tBu. For this purpose, the peptide (RRWQWRMKKLG) was simultaneously synthesized using 4-methylpiperidine or piperidine for Fmoc removal reagent. The obtained products had similar purities and yields. Finally, 21 peptides were synthesized using 4-methylpiperidine. Our results suggest that is possible to obtain synthetic peptides efficiently by the strategy SPPS-Fmoc/tBu when 4-methylpiperidine was used as reagent to remove Fmoc groups N-alpha protected amino acids.

Downloads

Download data is not yet available.

Author Biographies

Javier Eduardo García Castañeda, Universidad Nacional de Colombia

Departamento de Farmacia

Cristian Francisco Vergel Galeano, Universidad Nacional de Colombia

Departamento de Farmacia

Zuly Jenny Rivera Monroy, Universidad Nacional de Colombia

Departmento de Química, Facultad de Ciencias

Javier Eduardo Rosas Pérez, Universidad Nacional de Colombia

Departamento de Farmacia

References

Merrifield, R.B. J. Am. Chem. Soc. 1963, 85, 2149-2154.

Carpino, L.A. Acc. Chem. Res. 1987, 20, 401-407.

Carpino, L.A.; Han, G.Y. J. Am. Chem. Soc. 1970, 92, 5748-5749.

Athertohn, E.; Fox, H.; Harkissc, D.; Logan, J.C.; Sheppard, R.C; Williams, B.J. J. Chem. Soc., Chem. Commun. 1978, 13, 537-539.

Carpino, L.A.; Han, G.Y. J Org. Chem. 1972, 37, 3404-3409.

Fields, G.; Noble, R. Int. J. Peptide Protein Res. 1990, 35, 161-214.

Larsen, B.; Holm, A. Int. J. Peptide Protein Res. 1994, 43, 1-9.

Zinieris, N.; Leondiadis, L.; Ferderigos, N. J. Comb. Chem. 2005, 7, 4-6.

Várady, L.; Rajur, S.; Nicewonger, R.; Guo, M.; Ditto, L. J. Chrom. A. 2000, 869, 171-179.

Bodanszky, M.; Deshmane, S.; Martinez, J. J. Org. Chem. 1979, 44, 1622-1625.

Rawer, S.; Roeder, R.; Henklein, P. J Pept Sci. 2006, 12, Issue S1. 29th European Peptide Symposium.

Orain, D.; Ellard, J.; Bradley, M. J. Comb. Chem. 2002, 4, 1-16.

Sheppeck, J.E.; Kar, H.; Hong, H. Tetrah. Lett. 2000, 41, 5329-5333.

Isidro-Llobet, A.; Alvarez, M.; Albericio, F. Chem. Rev. 2009, 109, 2455-2504.

Carpino, L.A.; Sadat-Aalaee, D.: Beyermann, M. J. Org. Chem. 1990, 55, 1673-1675.

Beyermann, M.; Bienert, M.; Niedrich, H.; Carpino, L.; Sadat-Aalaee, D. J. Org. Chem. 1990, 55, 721-728.

Hachmann, J.; Lebl, M. J. Comb. Chem. 2006, 8, 149.

Shiryaev, S.; Kozlov, I.; Ratnikov, B.; Smith, J.; Lebl, M.; Strongin, A.Y. Biochem. J. 2007, 401, 743-752.

Sarin, V.K.; Kent, S.B.; Tam, J.P.; Merrifield, R.B. Anal.Biochem. 1981, 117, 147-157.

Jensen, J.K.; Alsina, J.; Songster, F.M.; Vagner, J.; Albericio, F.; Barany, G.J. Am. Chem. Soc. 1998, 120, 5441.

Downloads

Published

2017-10-12

Issue

Section

Regular Articles