Self-assembled nanostructures of long-acting GnRH analogs modified at position 7.
J Pept Sci
; 20(11): 868-75, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25053524
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Hormônio Liberador de Gonadotropina
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Pept Sci
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China