Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 138, Issue 34, Pages 10758-10761Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.6b06075
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Funding
- NIH [CA142746]
- W. M. Keck Foundation
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We report that phosphotyrosine-cholesterol conjugates effectively and selectively kill cancer cells, including platinum-resistant ovarian cancer cells. The conjugate increases the degree of noncovalent oligomerization upon enzymatic dephosphorylatdon in aqueous buffer. This enzymatic conversion also results in tike assembly of the cholesterol conjugates inside and outside cells and leads to cell death. Frelimiriary mechanistic studies suggest that the formed assemblies of the conjugates not only interact with actin filaments and midrotubules but also affect lipid rafts. As the first report of multifaceted supramolecular assemblies of cholesterol conjugates against cancer cells, this work illustrates the integration of enzyme catalysis and self-assembly of essential biological small molecules on and inside cancer cells as a promising strategy for developing multifunctional therapeutics to treat drug-resistant cancers.
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