Incorporation of Cα-methyl amino acids by solid phase peptide synthesis in a peptide sequence

Tetrahedron Letters

Volumn 37, Issue 37, 1996, Pages 6713-6716

  Brunissen, Alié ^a   Ayoub, Mimoun ^a,b   Lavielle, Solange ^a  

^a CNRS   (France)

^b Propeptide BP 12 ^*  (France)

Author keywords

[No Author keywords available]

Indexed keywords

SUBSTANCE P; SUBSTANCE P DERIVATIVE;

ARTICLE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; PEPTIDE SYNTHESIS; REACTION ANALYSIS; TECHNIQUE; THIN LAYER CHROMATOGRAPHY;

EID: 0030577006     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(96)01507-9     Document Type: Article

References (21)

1. 1. Toniolo, C. ; Crisma, M. ; Formaggio, F. ; Valle, G. ; Cavicchioni, G. ; Précigoux, G. ; Aubry, A. ; Kamphuis, J. Biopolymers, 1993, 33, 1061-1072.
2. 2. Hruby, V.J. In : Peptides, Chemistry, Structure and Biology, Proceedings of the 13th American Peptide Symposium, (Hodges, R.S. ; Smith, J.A. ; eds), 1994, ESCOM, Leiden, pp 3-17.
3. 3. Turk, J. ; Panse, G.T. ; Marshall, G.R. J. Org. Chem., 1975, 40, 953-955.
4. 4. Toniolo, C. ; Pantano, M. ; Formaggio, F. ; Crisma, M. ; Aubry, A. ; Bayeul, D. ; Précigoux, G. ; Dautant, A. ; Boesten, W.H.J. ; Schoemaker, H.E. ; Kamphuis, J. In : Peptides, Chemistry, Structure and Biology, Proceedings of the 13th American Peptide Symposium, (Hodges, R.S. ; Smith, J.A. ; eds), 1994, ESCOM, Leiden, pp 315-316.
5. 5. Karle, I.L. In : Peptides, Chemistry, Structure and Biology, Proceedings of the 14th American Peptide Symposium, (Kaumaya, P.T.P. ; Hodges, R.S. ; eds), 1996, ESCOM, Leiden, in press.
6. 6. Ayoub, M. ; Chassaing, G. ; Loffet, A. ; Lavielle, S. Tetrahedron Lett., 1995, 36, 4069-4072.
7. 7. Chassaing, G. ; Convert, O. ; Lavielle, S. Biochim. Biophys. Acta, 1986, 575, 397-404.
8. 8. Lavielle, S.; Chassaing, G.; Julien, S.; Besseyre, J.; Marquet, A.; Beaujouan, J.-C.; Torrens, Y.; Glowinski, J., Neuropeptides, 1986, 7, 191-200.
9. 9. Abbreviations : DCC : dicyclohexylcarbodiimide, HOBt : 1-hydroxybenzotriazole ; BOP : benzotriazole-1-y1-oxy-tris-pyrrolidinophosphonium hexafluorophosphate ; NEt3 : triethylamine ; NMP : N-methylpyrrolidone; Aib : 2-amino isobutyric acid ; TEAP : triethylammonium phosphate buffer.
10. 10. After Boc deprotection, the ninhydrin test of αMe amino acid is negative, coupling can be monitored with picric acid either qualitatively (yellow beads) or quantitatively (Gisin test extended to αMe amino acids).
11. 11. Bambino, F. ; Brownlee, R.T.C. ; Chin, F.C.K. Tetrahedron Lett., 1994, 4615-4618.
12. 12. Kricheldorf, H.R., Liebigs Ann. Chem., 1972, 765, 17-38.
13. 13. Bolin, D.R. ; Sytwu, I.I. ; Humiec, F. ; Meienhofer, J. Int. J. Peptide Protein Res., 1989, 33, 353-359.
14. 14. Anteunis, M.J.O.; Belu, C. Bull. Soc. Chim. Belg., 1987, 96, 119.
15. 2, NMP), the Boc-protected amino acid previously activated for 5 min with DCC/HOBt, 1 equiv. in NMP, was reacted for 3 hours at room temperature. A 5-molar excess of Boc-αMe amino acid and a 10-molar excess of non methylated amino acid were used.
16. 16. Gisin, B.F. Anal. Chem. Acta, 1972, 58, 248-249.15.
17. 17. Carpino, L.A.; El-Faham, A.; Albericio, F.; J. Chem; Soc., Chem. Commun., 1994, 201.
18. 18. Carpino, L.A.; Sadat-Aalae, D.; Chao, H.G.; DeSelms, R.H. J. Am. Chem. Soc., 1990, 772, 9650-9652.
19. 19. Similarly, Bienert et al. did not succeed in the preparation of Boc-α-Me amino acid-fluoride, personal communication.
20. 20. Peptides were purified by preparative reverse-phase HPLC on a 10-x250-mm Brownlee column packed with Aquapore octyl 300 A° pore size. The separation was accomplished with various gradients in aqueous 0.1% TFA at a flow rate of 6 ml/min with UV detection fixed at 220 nm. Before pooling, the collected fractions were cheked for purity by analytical HPLC. The separation was accomplished on a Lichrospher 100 RP-8e column at a flow rate of 1.5 ml/min in isocratic mode (solvent A; 0.25 M triethylammonium phosphate buffer, pH 3.0, solvent B: 60% acetonitrile in solvent A), with UV detection fixed at 210 nm.
21. 21. Wenschuh, H.; Beyerman, M.; Winter, R.; Bienert, M.; Ionescu, D.; Carpino, L.A. Tetrahedron Lett. 1996, in press.