A superior drug carrier - aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne
by Shanmuganathan, A.; Kumar, T. K. S.; Huang, C. M.; Yu, C.; Chin, D. H.
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 H-1-N-15 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.
- Journal
- Journal of Biomedical Science
- Volume
- 16
- Year
- 2009
- URL
- https://dx.doi.org/10.1186/1423-0127-16-48
- ISBN/ISSN
- 1423-0127; 1021-7770
- DOI
- 10.1186/1423-0127-16-48