An assessment of the mutational load caused by various reactions used in DNA encoded libraries
Bioorganic & Medicinal Chemistry, ISSN: 0968-0896, Vol: 52, Page: 116508
2021
- 16Citations
- 27Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations16
- Citation Indexes16
- 16
- Captures27
- Readers27
- 27
Article Description
DNA encoded libraries have become an essential hit-finding tool in early drug discovery. Recent advances in synthetic methods for DNA encoded libraries have expanded the available chemical space, but precisely how each type of chemistry affects the DNA is unstudied. Available assays to quantify the damage are limited to write efficiency, where the ability to ligate DNA onto a working encoded library strand is measured, or qPCR is performed to measure the amplifiability of the DNA. These measures read signal quantity and overall integrity, but do not report on specific damages in the encoded information. Herein, we use next generation sequencing (NGS) to measure the quality of the read signal in order to quantify the truthfulness of the retrieved information. We identify CuAAC to be the worst offender in terms of DNA damage amongst commonly used reactions in DELs, causing an increase of G → T transversions. Furthermore, we show that the analysis provides useful information even in fully elaborated DELs; indeed we see that vestiges of the synthetic history, both chemical and biochemical, are written into the mutational spectra of NGS datasets.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0968089621005162; http://dx.doi.org/10.1016/j.bmc.2021.116508; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85119200277&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/34800876; https://linkinghub.elsevier.com/retrieve/pii/S0968089621005162; https://dx.doi.org/10.1016/j.bmc.2021.116508
Elsevier BV
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