The Formation of Oxytocin Dimers is Suppressed by the Zinc–Aspartate–Oxytocin Complex

Avanti, Christina and Hinrichs, Wouter L.J. and Casini, Angela and Eissens, Anko C. and Van Dam, Annie and Kedrov, Alexej and Driesen, Arnold J. M. and Frijlink, Henderik W. and Permentier, Hjalmar P. (2013) The Formation of Oxytocin Dimers is Suppressed by the Zinc–Aspartate–Oxytocin Complex. Journal of Pharmaceutical Sciences. ISSN 1520-6017 (Online ISSN)

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Official URL: http://onlinelibrary.wiley.com/doi/10.1002/jps.235...

Abstract

The aim of this study was to investigate the effect of divalent metal ions (Ca,Mg2+, and Zn2+) on the stability of oxytocin in aspartate buffer (pH 4.5) and to determine their interaction with the peptide in aqueous solution. Reversed-phase high-performance liquid chromatography and high-performance size-exclusion chromatography measurements indicated that after 4 weeks of storage at 55◦C, all tested divalent metal ions improved the stability of oxytocin in aspartate-buffered solutions (pH 4.5). However, the stabilizing effects of Zn2+ were by far superior compared with Ca2+ andMg2+. Liquid chromatography–tandem mass spectrometry showed that the combination of aspartate and Zn2+ in particular suppressed the formation of peptide dimers. As shown by isothermal titration calorimetry, Zn2+ interacted with oxytocin in the presence of aspartate buffer, whereas Ca2+ or Mg2+ did not. In conclusion, the stability of oxytocin in the aspartate-buffered solution is strongly improved in the presence of Zn2+, and the stabilization effect is correlated with the ability of the divalent metal ions in aspartate buffer to interact with oxytocin. The reported results are discussed in relation to the possible mode of interactions among the peptide, Zn2+, and buffer components leading to the observed stabilization effects.

Item Type: Article
Uncontrolled Keywords: stability; oxytocin; zinc ions; aspartate buffer; aqueous; formulation; peptide; degradation; kinetic
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Pharmacy > Department of Pharmacy
Depositing User: Perpustakaan UBAYA
Date Deposited: 19 Apr 2013 04:20
Last Modified: 19 Apr 2013 04:20
URI: http://repository.ubaya.ac.id/id/eprint/3362

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