Metal-mediated base pairing within the simplified nucleic acid GNA

Area of Science:

• Synthetic biology
• Nucleic acid chemistry
• Biochemistry

Background:

• Glycol nucleic acid (GNA) is an artificial nucleic acid.
• Metal-dependent base pairing is crucial for nucleic acid function.
• Hydroxypyridone and pyridopurine bases are known to form metallo-base pairs.

Purpose of the Study:

• To investigate hydroxypyridone and pyridopurine base pairs in GNA.
• To synthesize phosphoramidites for automated GNA solid-phase synthesis.
• To evaluate the metal-dependent properties and stability of these base pairs in GNA.

Main Methods:

• Economical synthesis of phosphoramidites from enantiopure glycidol.
• Automated GNA solid-phase synthesis.
• Analysis of metal-dependent base pairing, stability, and selectivity.

Main Results:

• Hydroxypyridone and pyridopurine homo- and hetero-base pairs were successfully incorporated into GNA.
• These metallo-base pairs exhibit metal-dependent pairing, with preferences for Cu(II) and Ni(II) ions, respectively.
• The hydroxypyridone homo-base pair and hydroxypyridone-pyridopurine hetero-base pair in GNA show significantly enhanced stability with copper(II) ions compared to A:T pairs in DNA.

Conclusions:

• Hydroxypyridone and pyridopurine bases form stable metallo-base pairs within GNA duplexes.
• These GNA metallo-base pairs display modulated metal-dependent properties compared to DNA.
• The enhanced thermal stability of these copper(II)-dependent GNA base pairs opens new possibilities for artificial nucleic acid applications.