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Investigation of unknown impurities in cyclic dermorphin analogue by HPLC-MS

Katarzyna E. Filip ,  Tomasz Giller ,  Elżbieta U. Stolarczyk ,  Katarzyna Sidoryk ,  Olga M. Michalak ,  Krzysztof Bańkowski 

Pharmaceutical Research Institute, Rydygiera 8, Warsaw 01-793, Poland

Abstract
Dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) is highly selective, μ-opioid receptor ligand. The synthesis, biological activity and conformations of several side-chain to side-chain cyclized dermorphin analogues, containing a carbonyl bridge, has been previously described [1, 2, 3]. The object of this study, ureidopeptide UP-1, also belongs to the mentioned group, however - in comparison with the described series of analogues - posses some new modification of the N-terminal segment.
Developed synthetic process led to peptide UP-1 having a good HPLC purity (above 96%, after purification by semi-preparative HPLC). Unfortunately, the overall yield of the synthesis was wery low. One of the possible reason is forming some unknown by-products. In crude ureidopeptide several impurities were detected by HPLC-UV and attempts to make structural assignment of these compounds by HPLC-MS-MS were the main goal of this work.
Two impurities were isolated by semi-preparative reversed-phase high performance liquid chromatography. Based on mass spectrometric data and synthetic specifics the structure of one impurity was confirmed. Founded on HPLC-MS-MS analysis the potential structures of the others process-related by-products were also proposed.

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

 

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Presentation: Poster at VIII Multidyscyplinarna Konferencja Nauki o Leku, by Katarzyna E. Filip
See On-line Journal of VIII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2012-03-27 12:52
Revised:   2012-03-30 16:56