Search for content and authors
 

New cyclic dermorphin analogues containing a carbonyl bridge

Jan Izdebski 1Ewa Witkowska 1Krzysztof Bańkowski 2Olga M. Michalak 2Katarzyna Sidoryk 2Ewa Szymanek 2Bożena Antkowiak 3Katarzyna E. Filip 2

1. Warsaw University, Department of Chemistry, Pasteura 1, Warsaw 02-093, Poland
2. Pharmaceutical Research Institute, Rydygiera 8, Warsaw 01-793, Poland
3. Military Institute of Hygiene and Epidemiology (MIHE), Kozielska 4, Warsaw 01-163, Poland

Abstract

The cyclic dermorphin analogues, containing a carbonyl bridge have already been published [1-3];  all of them were N-unsubstituted amides.

The object of this study was the synthesis of N-substituted amides of dermorphin cyclic analogues containing an ureido group (Formula I) in the hope of preparing more proteolytical stable and analgesic active peptides.

ureidopeptyd.png

For the synthesis of N-substituted amides both approaches were used: solid phase peptide synthesis (SPPS) and classical method in solution. SPPS was carried out on functionalized MBH-resin [4] whereas classical metod was found to be more convenient to prepare a series of differently substituted amides starting from a common synton(s). All analogues were purified by semi-preparative HPLC metod.

The resistence of all new peptides to proteolysis was demonstrated by high resolution mass spectroscopy (HR-MS) method which showed full stability (no degradation products)  during 24-hours incubation with chymotrypsin and pepsin. New analogues  showed also remarkable antinociceptic effect. 

REFERENCES

1. Filip K., Oleszczuk M., Pawlak D., Wójcik J., Chung N.N., Schiller P.W., Izdebski J. Potent side-chain to side-chain cyclized dermorphin analogues containing a carbonyl bridge. J. Peptide Sci. 2003; 9: 649–657.

2. Filip K., Oleszczuk M., Wójcik J., Chung N.N., Schiller P.W., Pawlak D., Zieleniak A., Parcińska A., Witkowska E., Izdebski J. Cyclic enkephalin and dermorphin analogues containing a carbonyl bridge. J. Peptide Sci. 2005; 11: 347–352.

3. Witkowska E., Nowakowski M., Oleszczuk M., Filip K., Ciszewska M., Chung N.N., Schiller P.W., Wójcik J., Izdebski J. Ureido group containing cyclic dermorphin(1–7) analogues: synthesis, biology and conformation. J. Peptide Sci. 2007; 13: 519–528.

4. A. Wiszniewska, D. Kunce, N.N. Chung, P.W. Schiller, J. Izdebski, 2003; Synthesis of peptido­mimetics: An evaluation of p-nitrophenyl carbamate of ethylenediamine,  Lett .Pept. Sci. 10:33-39

 

Legal notice
  • Legal notice:
 

Related papers

Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Krzysztof Bańkowski
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-28 09:34
Revised:   2012-03-30 17:15