High Pressure Liquid Chromatography Studies of the Reaction of Platinum Complexes with Peptides

Platinum complexes (cisplatin, carboplatin and oxaliplatin) are effective anticancer agents. However the major drawbacks of platinum chemotherapy are toxic side effects and resistance. The affinity of platinum complexes to sulfur donor ligands of side chains of methionine and cysteine amino acids was assumed to be responsible for toxicity and resistance. Recently, it was found that the reaction of platinum complex with proteins containing sulfur donor ligands could actually favor its anticancer activity. Copper transporter 1 (Ctr 1), a protein involved in the transport of copper into the cell, also helps in the influx of cisplatin by binding to N-terminal domain of Ctr 1 which is rich in methionine and histidine residues. A better understanding of how the size and shape of amine ligand, and leaving groups affect the reaction of platinum (II) complexes with methionine could give new ways to optimize its anticancer activity. This preliminary research focuses to answer this by HPLC-UV-VIS analysis of bulky platinum complexes including [Pt(dien)Cl]Cl, Pt(Me4en)(NO3)2 and Pt(en)(NO3)2 with two methionine containing small peptides that serve as models for protein interactions.

Name thesis:degree_name

Master of Science

Discipline thesis:degree_discipline

Department of Chemistry

Year

2010

Author dc:creator

• Muneeruddin, Khaja

Contributors dc:contributor

• Dr. Kevin Williams (Director), Dr. Darwin Dahl, Dr. Rajalingam Dakshinamurthy

• platinum
• complex compounds
• cancer chemotherapy
• radiation chemistry
• Amino Acids, Peptides, and Proteins
• Chemistry
• Complex Mixtures
• Radiology

Repository record dc:identifier

https://digitalcommons.wku.edu/theses/196

OAI identifier oai:identifier

oai:digitalcommons.wku.edu:theses-1198