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Despite advances in cancer therapy, the prognosis of glioma patients has remained poor. Cytochrome c (Cytc), an endogenous heme\u2010based protein, holds tremendous potential to treat gliomas because of its innate capacity to trigger apoptosis. To this end, a hybrid cytochrome c\u2010chlorotoxin (Cytc\u2010CTX) protein was biosynthesized to enable cellular uptake of the cell impenetrable Cytc using CTX transporters. A nucleotide sequence containing 1\u2009:\u20091 Cytc and CTX was constructed and separated by a hexahistidine\u2010tag and an enterokinase cleavage site. The sequence was cloned into a pBTR1 plasmid, expressed in <jats:italic>Escherichia coli<\/jats:italic>, purified via 2\u2010dimensional chromatography. The identity and size of the protein were determined by Western blot and mass spectrometry. Cytc in this soluble hybrid protein has similar structure and stability as human Cytc and the hybrid protein is endocytosed into a glioma cell line, while displaying potent cytotoxicity and a favorable therapeutic index. Its facile, low\u2010cost, and high yield synthesis, biocompatibility, and robustness suggest that the hybrid protein is a promising candidate for antiglioma drug evaluation.<\/jats:p>","DOI":"10.1002\/cmdc.202000373","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T07:38:35Z","timestamp":1601019515000},"page":"2185-2192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Cytochrome <i>c<\/i>\u2010Chlorotoxin Hybrid Protein as a Possible Antiglioma Drug"],"prefix":"10.1002","volume":"15","author":[{"given":"Louis J.","family":"Delinois","sequence":"first","affiliation":[{"name":"Chemistry Department Faculty of Natural Sciences of the University of Puerto Rico at R\u00edo Piedras  San Juan, Puerto Rico 00925 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold","family":"Pe\u00f3n","sequence":"additional","affiliation":[{"name":"Academia del Perpetuo Socorro High School  San Juan, Puerto Rico 00907 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan C.","family":"Villalobos\u2010Santos","sequence":"additional","affiliation":[{"name":"Biology Department Faculty of Natural Sciences of the University of Puerto Rico at R\u00edo Piedras  San Juan, Puerto Rico 00925 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josell","family":"Ram\u00edrez\u2010Paz","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Natural Sciences of the University of Puerto Rico at R\u00edo Piedras  San Juan, Puerto Rico 00925 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Miller","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Natural Sciences of the University of Puerto Rico at R\u00edo Piedras  San Juan, Puerto Rico 00925 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai H.","family":"Griebenow","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Natural Sciences of the University of Puerto Rico at R\u00edo Piedras  San Juan, Puerto Rico 00925 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2825-5235","authenticated-orcid":false,"given":"Arthur D.","family":"Tinoco","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Natural Sciences of the University of Puerto Rico at R\u00edo Piedras  San Juan, Puerto Rico 00925 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,20]]},"reference":[{"key":"e_1_2_7_1_1","first-page":"4","volume":"20","author":"Ostrom Q. 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