Synthesis of Ethyl N-[(2-Boc-Amino)-Ethyl] Glycinate and PNA Monomer Containing 5-Iodouracil

Abstract

Peptide nucleic acids, or PNAs, are oligonucleotide analogs in which the sugarphosphate backbone is replaced with a polyamide structure. The PNAs were first synthesized about more than 15 years ago, and have received great attention for their potential as a drug in antisense or antigene applications and as diagnostic and
biological tools.

The PNAs have several favorable particular nature and unique properties including resistance to the digestion of nucleases and proteases, high stability in serum and cell extracts, and strong affinity and specificity to complementary sequences of DNA and RNA that form single and double-stranded DNA or RNA targets.

PNAs constitute an attractive new class of applications introduced in cytogenetics used as a promising procedure for in situ hybridization assays. The PNA technology is already used as an essential tool in a wide range of research and diagnostic molecular protocols. During recent years, the new applications of PNAs have appeared in genetics and cytogenetics such as genome mapping, antigene therapy,
mutation detection or aneuploidy screening.

In this project, a convenient and economic synthesis of ethyl N-[(2-Boc-amino) ethyl] glycinate, together with its hydrochloride, was developed. These are key
intermediates for the synthesis of peptide nucleic acid monomers and are usually the necessity to prepare N (2-aminoethyl) glycine derivatives. We have found a reliable and easily scalable route to ethyl N-[(2-Boc-amino) ethyl] glycinate.

At the same time, the PNA monomer (thymine-monomer) successfully has been obtained by the reaction based on the reported method. The PNA monomer can be used in future synthesis of PNA oligomers. And also. the preparation of other PNA
monomers can be fulfilled referring to this development.

Finally, a modified uracil PNA monomer was also synthesized, which can be used for the synthesis of modified peptide nucleic acid by post-synthetic modification.
The internal modification of PNAs could conceivably modulate their
antisense/antigene efficacy and the potency of interruption of nucleic acid processing enzymes.

Date of Award	Aug 2006
Original language	English
Awarding Institution	Aston University