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Preparation of Oligomeric 2′-Deoxy-5-Fluorouridylate of Defined Length and Backbone Composition: A Novel Pro-Drug form of the Potent Anti-Cancer Drug 2′-Deoxy-5-Fluorouridylate |
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| Authors: | William H Gmeiner Parag Sahasrabudhe Richard T Pon Jacque Sonntag Shashikumar Srinivasan Patrick L Iversen |
| Institution: | 1. Eppley Cancer Institute, Omaha, University of Nebraska Medical Center , Omaha, NE, 68198-6805;2. Department of Pharmaceutical Sciences , University of Nebraska Medical Center , Omaha, NE, 68198-6805;3. Regional DNA Synthesis Laboratory , University of Calgary;4. Department of Pharmacology , University of Nebraska Medical Center , Omaha, NE, 68198-6805;5. Department of Pharmacology , University of Nebraska Medical Center , Omaha, NE, 68198-6805 |
| Abstract: | Abstract A recursive protection scheme for FdUMP is employed by synthesizing oligonucleotides consisting of only FdU. 3′-O-exonuclease action releases FdUMP and a shortened oligonucleotide from which further exonuclease action releases more FdUMP. Such oligonucleotides are more cytotoxic to H4IIe, mouse fibroblast, and metastatic mouse rumor cells than are equivalent concentrations of FdU monomer. |
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