The reversible acetylation of lysines is one of the best characterized epigenetic modifications. Its involvement in many key physiological and pathological processes has been documented in numerous studies. Lysine deacetylases (KDACs) and acetyltransferases (KATs) maintain the acetylation equilibrium at histones but also many other proteins. Besides acetylation, also other acyl groups are reversibly installed at the side chain of lysines in proteins. Because of their involvement in disease, KDACs and KATs were proposed to be promising drug targets, and for KDACs, indeed, five inhibitors are now approved for human use. While there is a similar level of evidence for the potential of KATs as drug targets, no inhibitor is in clinical trials. Here, we review the evidence for the diverse roles of KATs in disease pathology, provide an overview of structural features and the available modulators, including those targeting the bromodomains of KATs, and present an outlook.

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We present an acoustic ejection mass spectrometry (AEMS) setup for ESI-MS based sample injection at a sampling rate faster than current ESI and MALDI techniques. A modified acoustic droplet ejection system was combined with an open port interface and a modified ESI source. To simulate applications of drug metabolism and pharmacokinetics analysis and high-throughput screening campaigns, two stress tests were performed regarding ion suppression and system endurance in combination with minor sample preparation. Maximum sampling rate was 6 Hz for dextromethorphan and d3-dextrorphan (each 100 nM) for 1152 injections in 63 s at FWHM of 105 ms and %RSD of 7.7%/7.5% without internal standard correction. Enzyme assay buffer and crude dog plasma caused signal suppression of 51%/73% at %RSD of 5.7%/6.7% (n = 120) and stable OPI performance during 1100 injections. An endurance buffer revealed minor OPI pollution and constant signals for >25.000 injections (%RSD = 8.5%, n = 10,557). File list (5) download file view on ChemRxiv Manuscript Ultrahigh-Throughput ESI-MS.pdf (0.94 MiB) download file view on ChemRxiv SI Ultrahigh-Throughput ESI-MS.pdf (2.59 MiB) download file view on ChemRxiv CC BY-NC-ND 4.0.url (54.00 B) download file view on ChemRxiv Video S-2.mp4 (17.97 MiB) download file view on ChemRxiv Video S-1.mp4 (6.04 MiB)

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