Abstract
Synthetic modified nucleosides designed to pair in unusual ways with natural nucleobases have many potential applications in nucleic acid biochemistry. This overview lays the foundation for future protocol units on synthesis and application of unnatural bases, with particular emphasis on unnatural base analogs that mimic natural bases in size, shape, and biochemical processing. Topics covered including base pairs with alternative H‐bonding schemes, hydrophobic base pairs, degenerate bases, universal nucleosides, and triplex constituents.

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