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

Shanmuganathan, Aranganathan; Kumar, Thallapuranam; Huang, Chiy-Mey; Yu, Chin; Chin, Der-Hang

doi:10.1186/1423-0127-16-48

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

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.

Authors:

Shanmuganathan, Aranganathan ^[1]; Kumar, Thallapuranam ^[2]; Huang, Chiy-Mey ^[3]; Yu, Chin ^[4]; Chin, Der-Hang ^[3]

National Chung Hsing Univ., Taichung, Taiwan (China). Dept. of Chemistry; National Tsing Hua Univ., Hsinchu, Taiwan (China). Dept. of Chemistry
Univ. of Arkansas, Fayetteville, AR (United States). Dept. of Chemistry and Biochemsitry
National Chung Hsing Univ., Taichung, Taiwan (China). Dept. of Chemistry
National Tsing Hua Univ., Hsinchu, Taiwan (China). Dept. of Chemistry

Publication Date:: 2009-01-01

Sponsoring Org.:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

OSTI Identifier:: 1626248

Resource Type:: Accepted Manuscript

Journal Name:: Journal of Biomedical Science

Additional Journal Information:: Journal Volume: 16; Journal Issue: 1; Journal ID: ISSN 1423-0127

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Cell Biology; Research & Experimental Medicine

Citation Formats


                    Shanmuganathan, Aranganathan, Kumar, Thallapuranam, Huang, Chiy-Mey, Yu, Chin, and Chin, Der-Hang. A superior drug carrier – aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne.  United States: N. p., 2009. 
Web.  doi:10.1186/1423-0127-16-48.

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                    Shanmuganathan, Aranganathan, Kumar, Thallapuranam, Huang, Chiy-Mey, Yu, Chin, & Chin, Der-Hang. A superior drug carrier – aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne.  United States.  https://doi.org/10.1186/1423-0127-16-48

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                    Shanmuganathan, Aranganathan, Kumar, Thallapuranam, Huang, Chiy-Mey, Yu, Chin, and Chin, Der-Hang. Thu .  
"A superior drug carrier – aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne".  United States.  https://doi.org/10.1186/1423-0127-16-48.  https://www.osti.gov/servlets/purl/1626248.

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@article{osti_1626248,

  title        = {A superior drug carrier – aponeocarzinostatin in partially unfolded state fully protects the labile antitumor enediyne},

  author       = {Shanmuganathan, Aranganathan and Kumar, Thallapuranam and Huang, Chiy-Mey and Yu, Chin and Chin, Der-Hang},

  abstractNote = {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.},

  doi          = {10.1186/1423-0127-16-48},

  journal      = {Journal of Biomedical Science},

  number       = 1,

  volume       = 16,

  place        = {United States},

  year         = {2009},

  month        = {1}

}

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Works referencing / citing this record:

Thiols Screened by the Neocarzinostatin Protein for Preserving or Detoxifying its Bound Enediyne Antibiotic
journal, March 2012

Chi, Hung-Wen; Huang, Chun-Chi; Chin, Der-Hang
Chemistry - A European Journal, Vol. 18, Issue 20
DOI: 10.1002/chem.201102825

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

Abstract

Citation Formats

Thiols Screened by the Neocarzinostatin Protein for Preserving or Detoxifying its Bound Enediyne Antibiotic journal, March 2012

Thiols Screened by the Neocarzinostatin Protein for Preserving or Detoxifying its Bound Enediyne Antibiotic
journal, March 2012