One Among Millions: The Chemical Space of NucleicAcid-Like Molecules

Biology encodes hereditary information in DNA and RNA, which are finely tuned to their biological functions and modes of biological production. The central role of nucleic acids in biological information flow makes them key targets of pharmaceutical research. Indeed, other nucleic acid-like polymers can play similar roles to natural nucleic acids both in vivo and in vitro; yet despite remarkable advances over the last few decades, much remains unknown regarding which structures are compatible with molecular information storage. Chemical space describes the structures and properties of molecules that could exist within a given molecular formula or other classification system. Using structure generation methods, we explore nucleic acid analogues within the formula ranges BC3–7H5–15O2–4 and BC3–6H5–15N1–2O0–4, where B is a recognition element (e.g., a nucleobase). Other restrictions included two obligatory points of attachment for inclusion into a linear polymer and substructures predicting chemical stabilit...