Advertisement

Letters in Peptide Science

, Volume 9, Issue 2–3, pp 119–123 | Cite as

Assessment of new 6-Cl-HOBt based coupling reagents for peptide synthesis. Part 1: Coupling efficiency study

  • Giuseppina Sabatino
  • Barbara Mulinacci
  • Maria C. Alcaro
  • Mario Chelli
  • Paolo Rovero
  • Anna M. Papini
Article

Summary

The efficiency of a series of well-known coupling reagents (TBTU, HATU, and PyBOP) and of newin situ activating reagents (TCTU, HCTU, and DMTMM) was compared by synthesizing the 65–74 fragment of the Acyl Carrier Protein (H-Val-Gln-Ala-Ala-Ile-Asp-Tyr-Ile-Asn-Gly-NH2), containing ‘a difficult sequence’, as a test peptide, in a multiple peptide synthesizer. The longer sequence rMOG(35–55) was also synthesized. It was clear that the aminium salts are more efficient than the phosphonium salt (PyBOP) and that the new 6Cl-HOBt based reagents (HCTU and particularly TCTU) are very efficient, while DMTMM appeared to be not suitable for SPPS.

Key words

automatic solid-phase peptide synthesis coupling reagents HCTU TCTU 

Abbreviation

DMF

N,N-dimethylformamide

DMTMM

4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride

DMSO

dimethylsulfoxide

6Cl-HOBt

6-chloro-1-hydroxybenzotrizole

EDT

1,2-ethanedithiol

HATU

1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo(4,5-b) pyridinium 3-oxide hexafluorophosphate

HCTU

1-[bis(dimethylamino)methylene]-5-chloro-1H-benzotriazolium 3-oxide hexafluorophosphate

HOAt

1-hydroxy-7-azabenzotriazole

HOBt

1-hydroxybenzotrizole

LC-ESIMS

liquid chromatography electron spray-ionization mass spectrometry

NMM

N-methylmorpholine

NMP

1-methyl-2-pyrrolidinone

PyBOP

benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate

RP-HPLC

reverse phase high-performance liquid chromatography

SPPS

solid-phase peptide synthesis

TBTU

1-[bis(dimethylamino)methylene]-1H-benzotriazolium 3-oxide tetrafluoroborate

TCTU

1-[bis(dimethylamino)methylene]-5-chloro-1H-benzotriazolium 3-oxide tetrafluoroborate

TFA

trifluoroacetic acid

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Albericio, F. and Kates, S. A., In Solid-Phase Synthesis: A Practical Guide, S. A. Kates and F. Albericio (eds) Marcel Dekker, New York, 2000, pp. 275–330.Google Scholar
  2. 2.
    Albericio, F., Bofill, J. M., El-Faham, A. and Kates, S. A., J. Org. Chem., 63 (1998) 9678.CrossRefGoogle Scholar
  3. 3.
    Albericio, F., Bailén, M. A., Chinchilla, R., Dodsworth, D. J. and Nájera, C., Tetrahedron, 57 (2001) 9607.CrossRefGoogle Scholar
  4. 4.
    König, W. and Geiger, R., Chem. Ber., 103 (1970) 788.PubMedGoogle Scholar
  5. 5.
    Carpino, L. A., J. Am. Chem. Soc. 115 (1993) 4397.CrossRefGoogle Scholar
  6. 6.
    Carpino, L. A., El-Faham, A. Minor, C. A. and Albericio, F., J. Chem. Soc., Chem Commun. (1994) 201.Google Scholar
  7. 7.
    Knorr, R., Trzeciak, A., Bannwarth, W. and Gillessen, D., Tetrahedron Lett., 30 (1989) 1927.CrossRefGoogle Scholar
  8. 8.
    Castro, B., Dormoy, J. R., Evin, G. and Selve, C., Tetrahedron Lett., (1975) 1219.Google Scholar
  9. 9.
    Israeli Patent Application No: IL 141804.Google Scholar
  10. 10.
    Kaminski, Z. J., Paneth, P. and Rudzinki, J., J. Org. Chem., 63, (1998) 4248.CrossRefGoogle Scholar
  11. 11.
    Falchi, A., Giacomelli, G., Porcheddu, A. and Taddei, M., Synlett, (2000) 275.Google Scholar
  12. 12.
    Atherton, E. and Sheppard, R. C., In: Solid Phase Peptide Synthesis: A Practic 1. Approach, D. Rickwood and B. D. Hames (eds), IRL Press, Oxford, 1989, p. 117.Google Scholar
  13. 13.
    Kunishima, M., Kawachi, C., Morita, J., Terao, K., Iwasaki, F. and Tani, S., Tetrahedron, 55 (1999) 13159.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Giuseppina Sabatino
    • 1
    • 2
  • Barbara Mulinacci
    • 1
    • 2
  • Maria C. Alcaro
    • 1
    • 2
  • Mario Chelli
    • 1
    • 2
  • Paolo Rovero
    • 3
  • Anna M. Papini
    • 1
    • 2
  1. 1.Dipartimento di Chimica Organica ‘Ugo Schiff’Università di FirenzeSesto Fiorentino (FI)Italy
  2. 2.Polo ScientificoCNR-ICCOMSesto Fiorentino (FI)Italy
  3. 3.Departmento di Scienze FarmaceuticheUniversità di SalernoFisciano (SA)Italy

Personalised recommendations