Initial Studies on a Novel Target-Promoted DNA Alkylation System

A novel target-promoted DNA alkylation system was designed, which consists of a DNA intercalating/alkylating quinone methide (QM) precursor, a removable amine linker, and a sequence-specific delivery. The QM in this system was regenerated by eliminating the amino linker promoted by the hydrophobic interaction between the target DNA and the intercalating QM precursor. Three alkylation model systems (methoxyl polycyclic system, intramolecular hydrogen bonding system and biaryl system) were proposed and synthesized. The potential DNA QM alkylation was investigated by deoxyadenosine (dA) and deoxyguanosine (dG) alkylation with the biaryl system. Only one deoxynucleoside adduct was observed when dA or dG reacted with quinoline or naphthalene QM precursor, in which both dA adducts degraded with time, while dG adducts remained unchanged after 72h at room temperature. The quinoline dG adduct was fully characterized as quinoline dG N1 adduct by NMR techniques. Naphthalene dG was found as a 1:1 mixture of diastereomers.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Chemistry

Year dc:date.available

2007

Author dc:creator

• Xu, Ting

Contributors dc:contributor

• Dr. Qibing Zhou

• cellular biology
• biaryl system
• intramolecular hydrogen bonding
• methoxyl polycyclic system
• alkylation
• quinone methide
• Chemistry
• Physical Sciences and Mathematics

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/714

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1713