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|標題:||A superior drug carrier - aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne||作者:||Shanmuganathan, A.
|關鍵字:||neocarzinostatin chromophore;molten globule;apo-neocarzinostatin;deoxyribonucleic-acid;beta-protein;intermediate;mechanism;binding;chromoprotein;spectroscopy||Project:||Journal of Biomedical Science||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.
|Appears in Collections:||化學系所|
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