Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/34478
標題: A superior drug carrier - aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne
作者: Shanmuganathan, A.
金德航
Kumar, T.K.S.
Huang, C.M.
Yu, C.
Chin, D.H.
關鍵字: neocarzinostatin chromophore
molten globule
apo-neocarzinostatin
deoxyribonucleic-acid
beta-protein
intermediate
mechanism
binding
chromoprotein
spectroscopy
期刊/報告no:: Journal of Biomedical Science, Volume 16.
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 (1)H-(15)N heteronuclear single quantum coherence spectroscopy. Results: The partially unfolded protein is in molten globule-like state, in which similar to 60% and similar to 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.
URI: http://hdl.handle.net/11455/34478
ISSN: 1021-7770
文章連結: http://dx.doi.org/10.1186/1423-0127-16-48
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