Synthetic strategies to improve the cytotoxicity of platinum-based cancer therapeutics
Citable URI:
http://hdl.handle.net/1721.1/36279
| Title: | Synthetic strategies to improve the cytotoxicity of platinum-based cancer therapeutics |
| Author: | Saouma, Caroline Thalia |
| Other Contributors: | Massachusetts Institute of Technology. Dept. of Chemistry. |
| Advisor: | Stephen J. Lippard. |
| Department: | Massachusetts Institute of Technology. Dept. of Chemistry. |
| Publisher: | Massachusetts Institute of Technology |
| Issue Date: | 2005 |
| Abstract: | The purpose of this thesis is to explore the conjugation of biomolecules to platinum(IV) compounds. Ever since the serendipitous discovery that cisplatin has cytotoxic properties in the 1970's, research has focused on both understanding the mode of action and making new potential drugs that have more desirable properties than cisplatin. Oxidizing cisplatin to platinum(IV) allows for the tethering of amines that can be used to target cancer cells. The first chapter is a brief introduction on the scope of platinum compounds that have been made. It also provides general background on the proposed mode of action. The second chapter adapts the knowledge of making cisplatin derived platinum(IV) complexes that are able to conjugate biomolecules, and adapts it to a second generation platinum drug, carboplatin. Furthermore, a method to make mono- or bis- substituted conjugates is devised. Chapter three describes the tethering of a series of estrogen linkers to oxidized derivatives of carboplatin, in hopes of seeing increased toxicity in ER(+) cells. This work mimics previous work in our lab which dealt with the tethering of estrogen to oxidized derivatives of cisplatin. Finally, in chapter four platinum-folate conjugates are described. Because cancer cells grossly overexpress folate receptors, tethering folic acid to platinum(IV) is desirable as it will allow for increased uptake in cancer cells. |
| Description: |
Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. Includes bibliographical references (p. 73-75). |
| URI: |
http://dspace.mit.edu/handle/1721.1/36279
http://hdl.handle.net/1721.1/36279 |
| Requires | CDROM contains copy of thesis in .pdf format. |
| Keywords: | Chemistry. |
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