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