A group of drug researchers has lost a pair of 2020 papers for a lack of reproducibility and other problems, including the unfortunate mislabeling of murine stem cells as having come from humans. (In case you’re wondering, mouse and human stem cells are at once quite similar and highly divergent.)
One article, “Divergent synthesis of 5-substituted pyrimidine 2′-deoxynucleosides and their incorporation into oligodeoxynucleotides for the survey of uracil DNA glycosylases,” appeared in Chemical Science. The second, “Convenient synthesis of pyrimidine 2′-deoxyribonucleoside monophosphates with important epigenetic marks at the 5-position,” was published in Organic & Biomolecular Chemistry. Both journals belong to the Royal Society of Chemistry.
The senior author on the papers was Yana Cen, a medicinal chemist now at Virginia Commonwealth University in Richmond. Cen has not responded to a request for comment.
According to the abstract of the Chemical Science paper:
Recent studies have indicated that 5-methylcytosine (5mC) residues in DNA can be oxidized and potentially deaminated to the corresponding thymine analogs. Some of these oxidative DNA damages have been implicated as new epigenetic markers that could have profound influences on chromatin function as well as disease pathology. In response to oxidative damage, the cells have a complex network of repair systems that recognize, remove and rebuild the lesions. However, how the modified nucleobases are detected and repaired remains elusive, largely due to the limited availability of synthetic oligodeoxynucleotides (ODNs) containing these novel DNA modifications. A concise and divergent synthetic strategy to 5mC derivatives has been developed. These derivatives were further elaborated to the corresponding phosphoramidites to enable the site-specific incorporation of modified nucleobases into ODNs using standard solid-phase DNA synthesis. The synthetic methodology, along with the panel of ODNs, is of great value to investigate the biological functions of epigenetically important nucleobases, and to elucidate the diversity in chemical lesion repair.
But the retraction notice states that efforts to confirm the findings foundered:
The Royal Society of Chemistry hereby wholly retracts this Chemical Science article due to concerns about the reproducibility of the data.
The Royal Society of Chemistry has been contacted by the authors of this article to alert us that recent experiments by their group have shown that some results are not reproducible, especially the yields of several key intermediates. Given the focus on the easy access to epigenetically important nucleosides and related ODNs, unreliable yields significantly impact the confidence in the results. In addition, it was discovered that one of the biological samples provided to the authors was mislabelled. The human stem cells were actually mouse stem cells, hence some discussion and conclusions in the article may no longer apply. Ahead of a thorough re-examination of the entire study, in order to preserve the rigor of the scientific record, the signing authors have chosen to retract the article and they would like to apologise for any inconvenience this may have caused for readers.
The notice is similar for the retraction in Organic & Biomolecular Chemistry, albeit without the mouse-man mixup:
The Royal Society of Chemistry hereby wholly retracts this Organic & Biomolecular Chemistry article due to concerns about the reproducibility of the data.
The Royal Society of Chemistry has been contacted by the authors of this article to alert us that recent experiments by their group have shown that some results are not reproducible, especially the yields of several key intermediates. Given the focus on the easy access to epigenetically important nucleoside monophosphates, unreliable yields significantly impact confidence in the results. Ahead of a thorough re-examination of the entire study, in order to preserve the rigor of the scientific record, the signing authors have chosen to retract the article and they would like to apologise for any inconvenience this may have caused for readers.
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