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Identification Of Cisplatin-Binding Proteins Using Agarose Conjugates Of Platinum Compounds, Takatoshi Karasawa, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger Jun 2013

Identification Of Cisplatin-Binding Proteins Using Agarose Conjugates Of Platinum Compounds, Takatoshi Karasawa, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger

Chemistry Faculty Publications and Presentations

Cisplatin is widely used as an antineoplastic drug, but its ototoxic and nephrotoxic side-effects, as well as the inherent or acquired resistance of some cancers to cisplatin, remain significant clinical problems. Cisplatin’s selectivity in killing rapidly proliferating cancer cells is largely dependent on covalent binding to DNA via cisplatin’s chloride sites that had been aquated. We hypothesized that cisplatin’s toxicity in slowly proliferating or terminally differentiated cells is primarily due to drug-protein interactions, instead of drug-DNA binding. To identify proteins that bind to cisplatin, we synthesized two different platinum-agarose conjugates, one with two amino groups and another with two chlorides …


Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui Feb 2013

Dimethyl Sulfoxide (Dmso) Exacerbates Cisplatin-Induced Sensory Hair Cell Death In Zebrafish (Danio Rerio), Phillip M. Uribe, Melissa A. Mueller, Julia S. Gleichman, Matthew D. Kramer, Qi Wang, Martha Sibrian-Vazquez, Robert M. Strongin, Peter S. Steyger, Douglas A. Cotanche, Jonathan I. Matsui

Chemistry Faculty Publications and Presentations

Inner ear sensory hair cells die following exposure to aminoglycoside antibiotics or chemotherapeutics like cisplatin, leading to permanent auditory and/or balance deficits in humans. Zebrafish (Danio rerio) are used to study drug-induced sensory hair cell death since their hair cells are similar in structure and function to those found in humans. We developed a cisplatin dose-response curve using a transgenic line of zebrafish that expresses membrane-targeted green fluorescent protein under the control of the Brn3c promoter/enhancer. Recently, several small molecule screens have been conducted using zebrafish to identify potential pharmacological agents that could be used to protect sensory hair cells …