- 作者: Aranganathan Shanmuganathan; Thallapuranam K. S. Kumar; Chiy-Mey Huang; Chin Yu; Der-Hang Chin
- 作者服務機構: Department of Chemistry, National Chung Hsing University, Taichung, Taiwan, Republic of China
- 中文摘要: --
- 英文摘要:
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 ~ 60% and ~ 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.
Conclusions :
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. - 中文關鍵字: --
- 英文關鍵字: --