Photochemically induced RNA and DNA abasic sites

Area of Science:

• Synthetic organic chemistry
• Nucleic acid chemistry
• Photochemistry

Background:

• Abasic sites are common DNA lesions that can be challenging to introduce synthetically.
• Controlled introduction of abasic sites is crucial for studying DNA repair and nucleic acid structure-function relationships.

Purpose of the Study:

• To develop novel phosphoramidite building blocks for the light-triggered synthesis of oligonucleotides containing abasic sites.
• To create building blocks that release both natural and modified abasic sites upon UV irradiation.

Main Methods:

• Synthesis of phosphoramidite building blocks incorporating photolabile protecting groups.
• Incorporation of these building blocks into oligoribonucleotides and oligodeoxyribonucleotides via automated synthesis.
• Photochemical deprotection using UV light to generate abasic sites.

Main Results:

• Successfully synthesized two phosphoramidite building blocks that efficiently generate natural abasic sites in both RNA and DNA upon UV deprotection.
• Developed a third building block capable of releasing a 2 acronym{'} -O-methylated abasic site following UV radiation.
• Demonstrated the compatibility of these building blocks with standard oligonucleotide synthesis protocols.

Conclusions:

• The developed phosphoramidite building blocks offer a versatile and efficient method for introducing abasic sites into nucleic acids.
• UV-triggered deprotection provides a mild and selective approach for abasic site generation.
• These tools will facilitate research in DNA repair, nucleic acid epigenetics, and the development of novel nucleic acid-based therapeutics.