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Synthesis and Investigation of Clickable and Cleavable Linkers for Drug Delivery

Bogen, William C
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1471347221

Abstract Details

2016, MS, University of Cincinnati, Arts and Sciences: Chemistry.
In the past several years, there has been a large focus placed on developing new methods for target-specific drug delivery. This focus is predominantly seen in the area of cancer therapeutics. Prognosis can be vastly increased if the drug only attacks and kills cancerous cells, leaving healthy cells alone. Two new compounds were designed and synthesized to investigate the ability of a specific oligonucleotide to recognize and bind overexpressed PSMA in C4-2 cells, a type of prostate cancer cell. These compounds were designed with a terminal alkyne for click coupling, a fluorescent label, and either a permanently attached or cleavable drug; diethylstilbestrol (DES) was chosen for this study. Successful synthesis of these two compounds has been verified by 1 H NMR, 13 C NMR, and MS. Four different compounds have been synthesized as a means to deliver cisplatin and carboplatin to the same cell type. These compounds were designed with either a terminal alkyne or azide for click coupling, either a linked cisplatin or carboplatin, with the linker being connected via and ester link. Synthesis of these compounds has been verified by 1H NMR, 13C NMR, and MS. Fluorescence in the cell-binding assays showed that both cleavable and non-cleavable DES were being delivered to the C4-2 cells. Toxicity studies showed that the non-cleavable DES had no significant cell toxicity, while the cleavable DES was toxic at concentrations of 7.50 µM and 3.75 µM. Toxicity studies on the cisplatin and carboplatin compounds have yet to be performed.
David Smithrud, Ph.D. (Committee Chair)
William Connick, Ph.D. (Committee Member)
Allan Pinhas, Ph.D. (Committee Member)
38 p.
Organic Chemistry
synthesis; drug delivery; cisplatin; carboplatin; click coupling; cleavable

Recommended Citations

Citations

  • Bogen, W. C. (2016). Synthesis and Investigation of Clickable and Cleavable Linkers for Drug Delivery [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1471347221

    APA Style (7th edition)

  • Bogen, William. Synthesis and Investigation of Clickable and Cleavable Linkers for Drug Delivery. 2016. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1471347221.

    MLA Style (8th edition)

  • Bogen, William. "Synthesis and Investigation of Clickable and Cleavable Linkers for Drug Delivery." Master's thesis, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1471347221

    Chicago Manual of Style (17th edition)

ucin1471347221
303
© 2016, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.