Selective Delivery of a Quinone Methide Precursor by Peptide Nucleic Acids

dc.contributor.advisorRokita, Steveen_US
dc.contributor.authorLiu, Yangen_US
dc.contributor.departmentChemistryen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2008-04-22T16:09:01Z
dc.date.available2008-04-22T16:09:01Z
dc.date.issued2007-12-10en_US
dc.description.abstractQuinone methides (QMs) are electrophilic intermediates that can be generated in vivo to alkylate DNA and function as anti-cancer drugs. Previously, DNA-QM conjugates have shown the ability to selectively deliver a QM to specific sequences of DNA. Peptide nucleic acids (PNAs) conjugates of QM are now being developed since PNA binds DNA with higher affinity than natural DNA. Synthesis of PNA oligomers and conjugation of the PNA to QM precursor are reported here. Synthesis of peptides was used to study the optimum conditions for preparation of the ultimate peptide-PNA conjugate. Both peptides and peptide-PNA have been synthesized after optimizing solid-phase techniques. Conditions for coupling a quinone methide precursor (QMP) and peptide-PNA conjugates were also evaluated. 8-Amino-3,6-dioxaoctanoic acid that links PNA and QMP is essential for coupling. MOPS buffer containing the peptide-PNA and an acetonitrile/dimethylformamide mixture containing QMP were combined for coupling. Finally, reactive QM derivative of peptide-PNA-QM was studied.en_US
dc.format.extent740014 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/1903/7809
dc.language.isoen_US
dc.subject.pqcontrolledChemistry, Organicen_US
dc.subject.pquncontrolledQMPen_US
dc.subject.pquncontrolledDNA alkylationen_US
dc.subject.pquncontrolledPNAen_US
dc.titleSelective Delivery of a Quinone Methide Precursor by Peptide Nucleic Acidsen_US
dc.typeThesisen_US

Files

Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
umi-umd-5092.pdf
Size:
722.67 KB
Format:
Adobe Portable Document Format