Editorial pubs.acs.org/acsmedchemlett
ACS Medicinal Chemistry Letters: Technology Notes a trifluoromethylated fluorocoxib A (B) fluorescence marker was used as a probe molecule to detect the cyclooxygenase-2 expression status in malignancies.2 A Technology Note on a new screening paradigm for glioblastoma treatment introduced a physiologically relevant high-throughput assay with patientderived cells grown as neurospheres and on laminin (C).3 Another drug-target screening strategy demonstrated the use of equilibrium dialysis in the presence and absence of the integrin αvβ6 receptor to detect high-affinity small molecule antagonists (D).4 Supercritical fluid chromatography (SFC) was used to assess the relative polarity profile of peptides, thus providing a convenient surrogate for permeability assays and serving as an indicator for intramolecular hydrogen bonding patterns in cyclopeptides (E).5 Furthermore, as an example for a new preparative technology, microfluidic electrosynthesis was shown to simulate CYP450 metabolism and enable the synthesis of drug metabolites (F).6 In summary, new toolbox innovations such as those highlighted above continuously drive medicinal chemistry forward and therefore define the current state-of-the-art of our field. In collaboration with ACS Combinatorial Science, Journal of Medicinal Chemistry, and Chemical Reviews, we chose a virtual issue collection that captures practical applications of techniques of interest to the medicinal chemistry community. For our part, we put the spotlight on recently published contributions to Technology Notes. ACS Medicinal Chemistry
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rogress in many areas of science is driven by new technologies. ACS Medicinal Chemistry Letters Technology Notes describe technical innovations that facilitate the practice of medicinal chemistry and are likely to become essential items in our toolbox. Noteworthy accomplishments are often based on the innovative use of new hardware developed for high throughput/high content screening, advances in structural biology instrumentation, flow chemistry techniques, parallel synthesis strategies, and improvements in process automation and miniaturization. Alternatively, new software developments in robotics, faster molecular modeling algorithms, and applications of artificial intelligence drive conceptual advances. Finally, the introduction of fundamentally new methods in structure- or fragment-based drug design, dynamic combinatorial chemistry, or synthesis tactics provide opportunities for the discovery of disruptive innovations. New synthetic tool compounds can also greatly enhance and broaden the information content of more traditional assay systems. Salient examples of peer-reviewed Technology Notes covering these areas have been published in ACS Medicinal Chemistry Letters over the past 3 years and include the development of a novel fluorescent probe (A) that can be used for the rapid measurement of the binding affinity of the cofactor αKG and ten-eleven translocation protein (Tet) inhibitors to Naegleria Tet1, a homologue to the mammalian DNA hydroxylase Tet (Figure 1).1 In a related approach,
Figure 1. Graphical overview of recent innovations featured in ACS Medicinal Chemistry Letters Technology Notes: Fluorescent probes (A1 and B2) for detection of small molecule inhibitors of epigenetic 5-methylcytosine oxidation and cyclooxygenase-2 expression status, respectively; a highthroughput screen3 for inhibitor sensitivity of laminin and neurosphere-grown glioblastoma cell lines (C); equilibrium dialysis4 for determination of integrin binding affinities (D); SFC as a relatively high-throughput tool5 to evaluate peptide permeability and intramolecular hydrogen bonding patterns (E); and a microfluidic electrochemical synthesis device (F)6 for the continuous-flow generation of drug metabolites. Published: January 12, 2017 © 2017 American Chemical Society
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DOI: 10.1021/acsmedchemlett.6b00484 ACS Med. Chem. Lett. 2017, 8, 1−2
ACS Medicinal Chemistry Letters
Editorial
Letters Technology Notes are an ideal medium to report and critically compare these advancements, highlight their innovative features, and propagate their use in the medicinal chemistry community.
Peter Wipf, Associate Editor
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Department of Chemistry, University of Pittsburgh
AUTHOR INFORMATION
Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS.
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REFERENCES
(1) Marholz, L. J.; Wang, W.; Zheng, Y.; Wang, X. A fluorescence polarization biophysical assay for the naegleria DNA hydroxylase Tet1. ACS Med. Chem. Lett. 2016, 7, 167−171. (2) Uddin, M. J.; Crews, B. C.; Huda, I.; Ghebreselasie, K.; Daniel, C. K.; Marnett, L. J. Trifluoromethyl fluorocoxib a detects cyclooxygenase-2 expression in inflammatory tissues and human tumor xenografts. ACS Med. Chem. Lett. 2014, 5, 446−450. (3) Quartararo, C. E.; Reznik, E.; Decarvalho, A. C.; Mikkelsen, T.; Stockwell, B. R. High-throughput screening of patient-derived cultures reveals potential for precision medicine in glioblastoma. ACS Med. Chem. Lett. 2015, 6, 948−952. (4) Tipping, W. J.; Tshuma, N.; Adams, J.; Haywood, H. T.; Rowedder, J. E.; Fray, M. J.; Mcinally, T.; Macdonald, S. J. F.; Oldham, N. J. Relative binding affinities of integrin antagonists by equilibrium dialysis and liquid chromatography-mass spectrometry. ACS Med. Chem. Lett. 2015, 6, 221−224. (5) Goetz, G. H.; Philippe, L.; Shapiro, M. J. EPSA: A novel supercritical fluid chromatography technique enabling the design of permeable cyclic peptides. ACS Med. Chem. Lett. 2014, 5, 1167−1172. (6) Stalder, R.; Roth, G. P. Preparative microfluidic electrosynthesis of drug metabolites. ACS Med. Chem. Lett. 2013, 4, 1119−1123.
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DOI: 10.1021/acsmedchemlett.6b00484 ACS Med. Chem. Lett. 2017, 8, 1−2
