Selective Delivery of a Quinone Methide Precursor by Peptide Nucleic Acids

Quinone 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…

Contents

Chapter 1: Introduction
1.1 Importance of DNA alkylation
1.2 DNA alkylation agents
1.3 Quinone Methides
1.4 PNAs function as sequence specific delivery agents
1.5 Function of telomerase and why choose telomerase as a target
Chapter 2: Synthesis of Peptide-PNA Conjugates
2.1 Introduction to solid-phase peptide synthesis
2.2 Result and discussion
2.2.1 Condtions for the synthesis of peptides
2.2.2 Synthesis of peptide-PNA conjugates
2.2.3 Conclusion
2.3 Experimental
2.3.1 General method
2.3.2 Materials
Chapter 3: Synthesis of Quinone Methide Precursor (QMP) and Coupling between QMP and Peptide-PNA Conjugates
3.1 Introduction
3.2 Result and discussion
3.2.1 Synthesis of QMP1
3.2.2 Conditions for coupling between a QMP1 analog and peptides
3.2.3 Conditions for coupling between Br-QMP, QMP and peptide-PNA
3.2.4 Formation of Peptide-PNA-QM self-adduct
3.2.5 Conclusion
3.3 Experimental
Chapter 4: Conclusion
Appendices

Author: Liu, Yang

Source: University of Maryland

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