Open AccessA Solution Phase Platform to Characterize Chemical Reaction Compatibility with DNA-Encoded Chemical Library Synthesis
Author(s) -
Anokha S. Ratnayake,
Mark E. Flanagan,
Timothy L. Foley,
Justin Donald Smith,
Jillian G. Johnson,
Justin Bellenger,
Justin I. Montgomery,
Brian M. Paegel
Publication year - 2019
Publication title -
acs combinatorial science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.928
H-Index - 81
eISSN - 2156-8952
pISSN - 2156-8944
DOI - 10.1021/acscombsci.9b00113
Subject(s) - chemistry , dna , compatibility (geochemistry) , fidelity , combinatorial chemistry , computational biology , nanotechnology , computer science , biochemistry , chemical engineering , telecommunications , materials science , engineering , biology
DNA-encoded chemical library (DECL) synthesis must occur in aqueous media under conditions that preserve the integrity of the DNA encoding tag. While the identification of "DNA-compatible" reaction conditions is critical for the development of DECL designs that explore previously inaccessible chemical space, reports measuring such compatibility have been largely restricted to methods that do not faithfully capture the impact of reaction conditions on DNA fidelity in solution phase. Here we report a comprehensive methodology that uses soluble DNA substrates that exactly recapitulate DNA's exposure to the chemically reactive species of DECL synthesis. This approach includes the assessment of chemical fidelity (reaction yield and purity), encoding fidelity (ligation efficiency), and readability (DNA compatibility), revealing the fate of the DNA tag during DECL chemistry from a single platform.