A superior drug carrier--aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne.
J Biomed Sci
; 16: 48, 2009 May 23.
Article
en En
| MEDLINE
| ID: mdl-19463188
ABSTRACT
BACKGROUND:
Neocarzinostatin is a potent antitumor drug consisting of an enediyne chromophore and a protein carrier.METHODS:
We characterized an intermediate in the equilibrium unfolding pathway of aponeocarzinostatin, using a variety of biophysical techniques including 1-anilino-8-napthalene sulfonate binding studies, size-exclusion fast protein liquid chromatography, intrinsic tryptophan fluorescence, circular dichroism, and 1H-15N heteronuclear single quantum coherence spectroscopy.RESULTS:
The partially unfolded protein is in molten globule-like state, in which approximately 60% and approximately 20% tertiary and secondary structure is disrupted respectively. Despite lacking a fully coordinated tertiary structure for assembling a functional binding cleft, the protein in molten globule-like state is still able to fully protect the labile chromophore. Titration of chromophore leads the partially denatured apoprotein to fold into its native state.CONCLUSION:
These findings bring insight into conserving mechanism of neocarzinostatin under harsh environment, where even the partially denatured apoprotein exhibits protective effect, confirming the superiority of the drug carrier.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Apoproteínas
/
Portadores de Fármacos
/
Cinostatina
/
Enediinos
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Biomed Sci
Asunto de la revista:
MEDICINA
Año:
2009
Tipo del documento:
Article
País de afiliación:
China