Self-assembled nanostructures of long-acting GnRH analogs modified at position 7
Version of Record online: 22 JUL 2014
Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Volume 20, Issue 11, pages 868–875, November 2014
How to Cite
2014), Self-assembled nanostructures of long-acting GnRH analogs modified at position 7, J. Pept. Sci., 20, pages 868–875. doi: 10.1002/psc.2678, , , , , and (
- Issue online: 20 OCT 2014
- Version of Record online: 22 JUL 2014
- Manuscript Accepted: 27 JUN 2014
- Manuscript Revised: 26 JUN 2014
- Manuscript Received: 20 MAR 2014
- Chinese National Science Foundation. Grant Number: 81172925
It is well known that GnRH analogs can self-assemble into amyloid fibrils and that the duration of action of GnRH analogs depends on the ability of the amyloid to slowly release active peptides. The aim of this study was to investigate the influence of the amino acid residues at position 7 of GnRH analogues on peptide self-assembly. It was found that the dominant shape of the nanostructure can be changed when the structures of the residues at position 7 differ significantly from that of leucine in Degarelix. When the backbone length was extended (peptide 9), or the side chain of the residue at position 7 was replaced by an aromatic ring (peptide 6), or the rotation of the amide bond was restricted (peptide 8), the nanostructure changed from fibrils to vesicles. The results also indicate that the increasing hydrophilicity had little influence on the nanostructure morphology. In addition, a suitable release rate was found to play a more important role for the duration of the peptide action by maintaining the equilibrium between the drug concentration and the persistent release time, while the nanostructure shape was found to exert little influence on the duration of the peptide action. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.