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Full-Text Articles in Physical Sciences and Mathematics
Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal
Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal
Chemistry & Biochemistry Faculty Publications
Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …
Interaction Of A Platinum Triamine Complex Having A Seven-Membered Chelate Ring With N-Acetyl-Lmethionine And Guanosine 5'-Monophosphate, Jae Ko
Masters Theses & Specialist Projects
In the 1960s, Rosenberg and his colleagues confirmed the anti-cancer activity of cisplatin. Although cisplatin was capable of killing testicular cancer cells there were also serious side effects. It was necessary to find alternate ways of overcoming side effects, and soon many researchers have discovered novel platinum compounds that show similar reactivity. Recently, replacing one chloride group to a heterocyclic amine group showed significant cytotoxicity with a different binding activity than cisplatin. Previously in our lab, [Pt(Me5dien)(NO3)]+ and [Pt(Et2dien)Cl]+ have been synthesized and reacted with NAcetyl- L-methionine (N-AcMet) and Guanosine 5’-monophosphate (5’-GMP) showed unusual reactivity. Unlike most previously studied platinum …
Effect Of Leaving Ligands Of Platinum(Ii) Diamine Complexes On Dna And Protein Residues, Ramya Kolli
Effect Of Leaving Ligands Of Platinum(Ii) Diamine Complexes On Dna And Protein Residues, Ramya Kolli
Masters Theses & Specialist Projects
Platinum compounds are widely used drugs in cancer treatments. Although DNA is the biological target, reaction of platinum compounds with proteins is also potentially significant. Our objective is to study the effects of leaving ligands on the relative reactivity between 5'-GMP (guanosine 5' phosphate), a key DNA target, and N-Acetyl - L-Methionine (N-AcMet), a key protein target. We have used NMR spectroscopy to monitor reactions with N-AcMet and 5'-GMP added to a platinum complex to see which products are formed preferentially. Previous research showed that both a non-bulky complex such as [Pt(en)(D2O)2]2+ [en=ethylenediamine], and a …
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
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 …
The Reaction Of Methionine With A Non-C2-Symmetrical Platinum (Ii) Diamine Compound, Nilesh Sahi
The Reaction Of Methionine With A Non-C2-Symmetrical Platinum (Ii) Diamine Compound, Nilesh Sahi
Mahurin Honors College Capstone Experience/Thesis Projects
The research that we have conducted has allowed us to discover that the amino acids, methionine (Met) and N-acetyl methionine (N-AcMet), will react in a 1:1 and 1:2 molar ratio with platinum complexes containing bulky diamine ligands. Previous research has allowed us to gain a plethora of information on the experimentation and results of specific bulky diamine ligands such as N,N,N',N'-tetramethylethylenediamine and N,N-diethylethylenediamine. In the current study, we have investigated the bulky diamine ligand of N,N-dimethylethylenediamine, or Me2en. With our focus on the bulk of the Me2en ligand, we have been able to synthesize a platinum …
Oxaliplatin And Oxaliplatin Derivatives: Synthesis, Characterization, And Reactivity With Biologically Relevant Ligands, Amy Poynter
Mahurin Honors College Capstone Experience/Thesis Projects
Oxaliplatin is a third generation anticancer drug that has proven to be successful in fighting ovarian and testicular cancer. We are interested in determining how oxaliplatin and oxaliplatin derivatives interact with proteins, as well as how that interaction is affected by the size and shape of these platinum compounds. We have synthesized oxaliplatin as it is used in cancer treatment, as well as similar platinum compounds with the same diaminocyclohexane ligand as oxaliplatin but with additional bulk added to the nitrogen atoms. We are reacting oxaliplatin with key amino acids, including methionine, and will be comparing the kinetics of this …
Inhibition Of Cysteine Protease By Platinum (Ii) Diamine Complexes, Chaitanya Rapolu
Inhibition Of Cysteine Protease By Platinum (Ii) Diamine Complexes, Chaitanya Rapolu
Masters Theses & Specialist Projects
Chemotherapy is the first line of treatment used in cancer. Chemotherapy drugs such as cisplatin, carboplatin and oxaliplatin are used in treatment. Cisplatin enters the cell through copper transporter CTR1 by passive diffusion and bind to DNA and proteins. Cisplatin is found to inhibit several enzymes targeting cysteine, histidine and methionine residues, which are expected to be responsible for its anticancer activity. A better understanding of how the size and shape and leaving ligands of platinum complexes affect cysteine protease, papain enzyme are studied. This could give new ways to optimize anticancer activity. The activity of papain enzyme was measured …