A comparison of histidine protecting groups in the synthesis of peptide- oligonucleotide conjugates

Tetrahedron Letters

Volumn 39, Issue 23, 1998, Pages 4115-4118

  Beltrán, Maite ^a   Pedroso, Enrique ^a   Grandas, Anna ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

HISTIDINE; NUCLEOPEPTIDE; OLIGONUCLEOTIDE; PEPTIDE; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; ARTICLE; CONJUGATION; HYBRIDIZATION; PEPTIDE SYNTHESIS; RNA TRANSLATION; SOLID PHASE EXTRACTION;

EID: 0032482495     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00669-8     Document Type: Article

References (23)

1. 1. Truffert, J-C.; Asseline, U.; Brack, A.; Thuong, N. T. Tetrahedron 1996, 52, 3005-3016.
2. 2. Hovinen, J.; Guzaev, A.; Azhayeva, E.; Azhayev, A.; Lönnberg, H. J. Org. Chem. 1995, 60, 2205-2209.
3. 3. Polushkin, N. N.; Chen, B-C.; Anderson, L. W.; Cohen, J. S. J. Org. Chem. 1993, 58, 4606-4613.
4. 4. Bashkin, J. K.; McBeath, R. J.; Modak, A. S.; Sample, K. R.; Wise, W. B. J. Org. Chem. 1991, 56, 3168-3176.
5. 5. Bashkin, J. K.; Gard, J. K.; Modak, A. S. J. Org. Chem. 1990, 55, 5125-5132.
6. 6. Abbreviations used: Aa= amino acid; Boc=t-butoxycarbonyl; Bz=benzoyl; CNE=2-cyanoethyl; DCM=dichloromethane; DIEA=diisopropylethylamine; DIPC=N,N′-diisopropylcarbodiimide; Dmf=dimethylaminomethylene; DMT=4,4′-dimethoxytrityl; dN=2′-deoxynucleoside; Dnp=2,4-dinitrophenyl; HOBt=1-hydroxybenzotriazole; Hse=homoserine; iBu=isobutyryl; NMI=N-methylimidazole; NPE=3-nitro-4-(2-ethoxy)benzoyl; Phac=phenylacetyl; TBAF=tetrabutylammonium fluoride; TCA=trichloroacetic acid; TFA=trifluoroacetic acid; THF=tetrahydrofuran; Tos=tosyl.
7. 7. Robles, J.; Pedroso, E.; Grandas, A. J. Org. Chem. 1994, 59, 2482-2486.
8. 8. Robles, J., Pedroso, E., and Grandas, A. Nucleic Acids Res. 1995, 23, 4151-4161.
9. 9. Barany, G.; Merrifield, R. B. Solid-Phase Peptide Synthesis. In The Peptides. Analysis, Synthesis, Biology (volume 2, Special Methods in Peptide Synthesis, part A) Gross, E.; Meienhofer, J., Eds. Academic Press; New York, 1980; pp. 179-189.
10. 10. Geiger, R.; König, W. Amine Protecting Groups. In The Peptides. Analysis, Synthesis, Biology (volume 3, Protection of Functional Groups in Peptide Synthesis) Gross, E.; Meienhofer, J., Eds. Academic Press; New York, 1981; pp. 70-80.
11. 11. Carreño, C.; Roig, X.; Cairó, J.; Camarero, J.; Mateu, M. G.; Domingo, E.; Giralt, E.; Andreu, A. Int. J. Peptide Protein Res. 1992, 39, 41-47.
12. 12. Fuji, T.; Sakakibara, S. Bull. Chem. Soc. Jpn. 1974, 47, 3146-3151.
13. 13. Beltrán, M.; Maseda, M.; Robles, J.; Pedroso, E.; Grandas, A. Lett. Pept. Sci. 1997, 4, 147-155.
14. 14. Stewart, J. M. and Young, J. D. In Solid Phase Peptide Synthesis (2nd ed.) Pierce Chemical Co.; Rockford (Illinois), 1984; p. 83.
15. 15. HF Treatment of Ac-Gly-Ala-Hse-His(Dnp)-Val-OPAM-resin afforded a sample of Ac-Gly-Ala-Hse-His(Dnp)-Val-OH. The sample of Ac-Gly-Ala-Hse-His-Val-OH was obtained after HF acidolysis of Ac-Gly-Ala-Hse-His(Tos)-Val-OPAM-resin.
16. 16. Fmoc-leucine was first anchored to an amino-functionalized solid support (p-methylbenzhydrylamine resin) to yield an amino acid-resin with a substitution degree suitable for the oligonucleotide elongation, and unreacted amino groups were acetylated. A piperidine treatment eliminated the Fmoc group, and coupling of 3-nitro-4-(2-hydroxyethyl)benzoic acid afforded the resin onto which the nucleopeptides were assembled.
17. 17. Grandas, A.; Jorba, X.; Giralt, E.; Pedroso, E. Int. J. Peptide Protein Res. 1989, 33, 386-390.
18. 3′dACTAGT)-His-Val-OH: gradient from 5 to 25% of B.
19. 19. A coloured organic impurity with the typical Dnp UV absorption may be found in the nucleopeptide crude, but uncoloured products are isolated after MPLC purification.
20. 11P: 703.61.
21. 21. In the case of nucleopeptide-resin with X=Tos, previous removal of the tosyl group by reaction with HOBt afforded a slightly cleaner crude.
22. 6: 2378.76.
23. +, virtually nil, was found in both cases (approx. 1%, probably due to some nucleoside adsorption on the polystyrene solid support).