Synthesis and triplex forming properties of pyrimidine derivative containing extended functionality

Area of Science:

• Synthetic organic chemistry
• Nucleoside chemistry
• Molecular biology

Background:

• Pyrimidine nucleosides are fundamental building blocks of DNA.
• Modifying nucleoside structure can alter DNA properties and functions.
• Developing novel nucleosides is crucial for advancing genetic engineering and diagnostics.

Purpose of the Study:

• To synthesize novel pyrimidine nucleosides with extended hydrogen bonding capabilities.
• To investigate the utility of these modified nucleosides in DNA synthesis.
• To evaluate the sequence-targeting specificity of the synthesized nucleosides.

Main Methods:

• Synthesis of two pyrimidine nucleoside analogues incorporating semicarbazide and monoacetylated carbohydrazide side chains.
• Adaptation of a reverse coupling protocol for DNA synthesis using the analogue nucleosides.
• Modification of the standard DNA synthesis protocol, including elimination of the capping step and replacement of the oxidizing agent.

Main Results:

• Successful synthesis of two pyrimidine nucleoside analogues with extended hydrogen bonding.
• Demonstration of DNA sequence preparation using both analogue nucleosides via a modified reverse coupling protocol.
• Observation of moderate selectivity in targeting C-G base pairs within polypurine sequences by the modified nucleosides.

Conclusions:

• Novel pyrimidine nucleosides with extended hydrogen bonding can be synthesized and incorporated into DNA.
• A modified DNA synthesis protocol is effective for utilizing these analogue nucleosides.
• These modified nucleosides show potential for specific targeting of C-G base pairs, opening avenues for new molecular tools.