The cost of publication in Journal of Biomedical Science is borne by the National Science Council, Taiwan.

Research

A superior drug carrier – aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne

Aranganathan Shanmuganathan^1,2 , Thallapuranam Krishnaswamy Suresh Kumar³ , Chiy-Mey Huang¹ , Chin Yu² and Der-Hang Chin¹

¹  Department of Chemistry, National Chung Hsing University, Taichung, Taiwan 40227, Republic of China

²  Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan 30013, Republic of China

³  Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701, USA

author email corresponding author email

Journal of Biomedical Science 2009, 16:48doi:10.1186/1423-0127-16-48

Published:	23 May 2009

Abstract

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.

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.