Синтез пептидных алкинов: изучение С-концевой модификации пептидов

In this paper, we report a straightforward strategy for alkynes modification at peptide C-terminus combining both solid phase and solution phase methods.  The cleavage under weak acidic conditions releases fully protected peptide fragments from the resin, which are then reacted with C-terminal units in solution, followed by removal of all protecting groups after the separation of the crude peptide alkynes.  This strategy is validated and presented with a group of medium-size peptide fragments and can be useful in the preparation of precursors for click chemistry. References. 1.    Tulla-Puche J., Barany G. / J. Org. Chem. 2004, 69, 4101-4107. 2.    Stewart J. M., Young J. D. / Solid phase peptide synthesis, 2nd Ed.— Pierce Chemical Company, Rockford, 1984, pp. 91. 3.    Wellings D. /Fmoc solid phase peptide synthesis: a practical approach // Eds. W. C. Chan, P. D. White — Oxford University Press, 2000. P. 146 . 4.    Hutchins S. M., Chapman K. T. /Tetrahedron Lett., 1996, 37, 4869-4872. 5.    Cheng Y., Chapman K. T. /Tetrahedron Lett., 1997, 38, 1497-1500. 6.    D?rner B., White P. / Peptides 1998, Proceedings of 25th European Peptide Symposium, Budapest, Akad?miai Kiad?, 1999, pp.90. 7.    Backes B. J., Ellman J. A. /J. Org. Chem., 1999, 64. 2322-2330. 8.    Lew A., Chamberlin A. R. /Bioorg. Med. Chem. Lett., 1999, 9, 3267-3272. 9.    Wang X., Porco J. A. / J Org. Chem. 2001, 66, 8215-8221. 10.    Ingenito R., Bianchi E., Fattori D., Pessi A. /J. Am. Chem. Soc., 1999, 121, 11369-11374. 11.    Shin Y., Winans K. A., Backes B. J., Kent S. B. H., Ellman J. A., Bertozzi C. R. /J. Am. Chem. Soc., 1999, 121, 11684-11689. 12.    Fattori D., Kinzel O., Ingallinella P., Bianchi E., Pessi A. /Bioorg. Med. Chem. Lett., 2002, 12, 1143-1147. 13.    Escher S. E., Kluver E., Adermann K. /Lett. Pept. Sci., 2001, 8, 349-357. 14.    Dawson P. E., Muir T. W., Clark-Lewis I., Kent S. B. / Science, 1994, 266, 776-779. 15.    Tam J. P., Lu Y-A., Liu C-F., Shao J. / Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 12485-12489. 16.    Mortensen U., Olesen K., Stennicke H., Sorensen S. B., Breddam. K./Modified Carboxypeptidase, United States Patent #5985627, 1999. 17.    Hoess E., Bordusa F., Herrmann R., Jakubke H., Tischer W./C-terminal modification of polypeptides, EP1778839. 18.     Hoess E., Bordusa F., Herrmann R., Jakubke H., Tischer W./C-terminal modification of polypeptides, WO/2006/015879. 19.    Kolb H. C., Finn M. G., Sharpless K. B. / Angew. Chem. Int. Ed. 2001, 40, 2004-2021.