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Full-Text Articles in Chemistry

Interaction Of A Platinum Triamine Complex Having A Seven-Membered Chelate Ring With N-Acetyl-Lmethionine And Guanosine 5'-Monophosphate, Jae Ko Oct 2019

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 …


Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs, Nathan Puckett Apr 2017

Effects Of Binding Affinity Between Bovine Serum Albumin And Platinum Drugs, Nathan Puckett

Masters Theses & Specialist Projects

Platinum complex drugs such as cisplatin have been used as highly successful chemotherapy drugs since the 1970s. We are interested in how the ligands attached to cisplatin analogs influences their reactivity with biologically relevant targets along with time and amount. For this study, reactions were conducted to determine the reactivity between different platinum compounds and the protein bovine serum albumin. Various platinum compounds with different ligands were reacted in varying amounts with albumin in ammonium acetate buffer for either 1 hour, 4 hours, or 24 hours. Each reaction was quenched after the designated reaction time by dialysis and the platinum …


Relative Reaction Rates Of The Amino Acids Cysteine, Methionine, And Histidine With Analogs Of The Anti-Cancer Drug Cisplatin, Cynthia A. Tope May 2015

Relative Reaction Rates Of The Amino Acids Cysteine, Methionine, And Histidine With Analogs Of The Anti-Cancer Drug Cisplatin, Cynthia A. Tope

Mahurin Honors College Capstone Experience/Thesis Projects

We are studying the reaction of analogs of the anticancer drug cisplatin with amino acids that differ in size and shape. The reaction of cisplatin with proteins likely precedes reaction with DNA in the body, forming a variety of products that may be toxic to the human body. The size and shape of the platinum(II) complexes often affects the rate of reaction with proteins, more so than with DNA. In this study, triamine cisplatin analogs are reacted with the amino acids cysteine, methionine, and histidine simultaneously. These reactions are monitored by NMR spectroscopy. The effect of the bulk of the …


The Interaction Of Glutathione With Platinum, And The Role Of Ph In Altering Ligand Formation Between Platinum And N-Acetylcysteine, Kyle B. Mann May 2015

The Interaction Of Glutathione With Platinum, And The Role Of Ph In Altering Ligand Formation Between Platinum And N-Acetylcysteine, Kyle B. Mann

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an important anti-cancer drug. Structurally, cisplatin is a coordination complex, which means that it has a central metallic atom: platinum. Side interactions prevent cisplatin from effectively treating cancerous cells by reaction with DNA. Cisplatin has a high rate of forming protein adducts, primarily with sulfur containing amino acids. To better understand how cisplatin interacts with sulfur containing amino acids in the body, a platinum compound with an ethylenediamine ligand attached was reacted with N-acetylcysteine and glutathione. The reactions of cysteine with platinum were performed at three pH values: 7.0, 8.5, and 10. NMR spectroscopy was used to examine …


Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan Dec 2014

Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan

Mahurin Honors College Capstone Experience/Thesis Projects

We are studying reactions of cisplatin derivatives, which differ in both size and shape, with various amino acids. When reaction with DNA occurs, apoptosis is observed, ideally leading to termination of the cancer. Due to the affinity of cisplatin for sulfur-containing amino acids, reaction with proteins may occur prior to access to the DNA, producing a large array of products, which could potentially be toxic to the human body. Both the size and shape of the platinum complexes often affect the reactions with protein targets more so than with DNA targets. By performing reactions of specific amino acids targets with …


Effect Of Leaving Ligands Of Platinum(Ii) Diamine Complexes On Dna And Protein Residues, Ramya Kolli May 2013

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 …


Reactions Of Platinum(Ii) Compounds With Selenium Containing Amino Acids, Stephanie Robey May 2013

Reactions Of Platinum(Ii) Compounds With Selenium Containing Amino Acids, Stephanie Robey

Masters Theses & Specialist Projects

Platinum(II) anticancer medications essentially react with DNA forming kinks in
the double helix of DNA and causing apoptosis. It has also been noted that these
anticancer medications react with methionine and cysteine in the body. With the new discoveries of selenium containing amino acids including selenomethionine and selenocysteine, new research is ongoing to see what types of products can be formed from these amino acids. Our research reacts [Pt(Met-S,N)Cl2] 2+ with selenomethionine to determine what types of products are produced. Monochelates including [Pt(SeMet-Se,N)Cl2] 2+ have formed two isomers, …


The Reaction Of Methionine With A Non-C2-Symmetrical Platinum (Ii) Diamine Compound, Nilesh Sahi May 2012

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 May 2012

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 …


Reactions With Platinum (Ll) Complexes And Selenium-Containing Amino Acids, Stephanie Robey Dec 2011

Reactions With Platinum (Ll) Complexes And Selenium-Containing Amino Acids, Stephanie Robey

Mahurin Honors College Capstone Experience/Thesis Projects

We have reacted [Pt(Me4en)(D2O)2]2+ [Me4En=N,N,N’N’-tetramethylethylenediamine] with Selenomethionine (SeMet), Methionine (Met), and Methylselenocysteine (MeSeCys). When MeSeCys was reacted with [Pt(Me4en)(D2O)2]2+, we observed both stereoisomers of Se,N chelates, as well as [Pt(Me4en)(MeSeCys)Cl]+ from ­1­H NMR Spectroscopy; the latter formed due to the presence of Cl- in the solution. Both isomers of the chelate seemed to form proportionally to one another, not favoring a specific stereoisomer. Eventually the [Pt(Me4en)(MeSeCys)Cl]+ products became Se,N chelates. We incubated SeMet with …


Inhibition Of Cysteine Protease By Platinum (Ii) Diamine Complexes, Chaitanya Rapolu Dec 2011

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 …


The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives, Yueh Ying Liao Apr 2010

The Reaction Of A Water Soluble Platinum Compound With Methionine And Derivatives, Yueh Ying Liao

Masters Theses & Specialist Projects

Water soluble platinum complexes are a recent area of emphasis of cisplatin chemistry. The water soluble complexes could have a reduced toxicity compared with cisplatin. Oxaliplatin, which has an oxalate leaving group, has previously been shown to have less nephro-toxicity and higher water solubility than cisplatin. [Pt(en)(oxalate)] (en = ethylenediamine) has been prepared from Pt(en)Cl2 and silver oxalate. This complex has been reacted with methionine and N-acetylmethionine at different molar ratios. At high Pt: methionine ratios, chelates with the sulfur and nitrogen atoms of the methionine are dominant; at lower Pt: methionine ratios, a bis-methionine product is formed. The en …