Two are not enough: synthetic strategies and applications of unnatural base pairs

Nucleic acid chemistry is a rapidly evolving field, and the need for novel nucleotide modifications and artificial nucleotide building blocks for diagnostic and therapeutic use, material science or for studying cellular processes continues unabated. This review focusses on the development and application of unnatural base pairs as part of an expanded genetic alphabet. Not only recent developments in nature-like artificial base pairs are presented, but also current synthetic methods to get access to C-glycosidic nucleotides. Wide-ranging viability in synthesis is a prerequisite for the successful use of unnatural base pairs in a broader spectrum and will be discussed.

Automated summary

Nucleic acid chemistry is constantly evolving to meet the demand for novel nucleotide modifications and artificial building blocks. This review focuses on the development and applications of unnatural base pairs in expanding the genetic alphabet. Recent advancements in nature-like artificial base pairs as well as synthetic methods for acquiring C-glycosidic nucleotides are presented. The feasibility of synthesis plays a vital role in the successful utilization of unnatural base pairs and is thoroughly discussed.