Preparation of ¹³C and ¹⁵N modified derivatives of Adenosine and 2ʹ-Deoxyadenosine.

Abstract

This project deals with synthesis ofmodified nucle ides and their incorporation into 10-base sequence DNA and RNA strands (oligomers). These DNA and RNA fragments possess the proper polarity to easily enter cells through the cell membranes. Enzymes within the cell cleave these molecules, releasing the modified nucleosides. In the present investigation, BC And l~ modified derivatives of adenosine and zt-deoxyadenosine were prepared. These derivatives are prepared to see the bond weakening between base pairs, adenine and 5-ftuoro-zt-deoxyuridine , which are incorporated into two respective strands of DNAorRNA. This would inhibit DNA replication resulting in the death of cancer cells. The studies are being conducted in Eppley Cancer Institute in Omaha, Nebraska to see their effect against various cancer cells and to study base pairing by Nuclear Magnetic Resonance (NMR) spectroscopy. The results of the present research showed the successful formation of unlabeled adenosine by a new synthetic methodology, which will be used to prepare labeled adenosine and BC enrichment at C8 of zt deoxyadenosine.