Dataset Information

Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP).

ABSTRACT: Target-identification and understanding of mechanism-of-action (MOA) are challenging for development of small-molecule probes and their application in biology and drug discovery. For example, although aspirin has been widely used for more than 100 years, its molecular targets have not been fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the following two parts: (i) activity-based protein profiling (ABPP) and iTRAQ™ quantitative proteomics for identification of target proteins and (ii) acid-cleavable linker-based ABPP for identification of peptides with specific binding sites. It is known that reaction of aspirin with its target proteins leads to acetylation. We thus applied the above technique using aspirin-based probes in human cancer HCT116 cells. We identified 1110 target proteins and 2775 peptides with exact acetylation sites. By correlating these two sets of data, 523 proteins were identified as targets of aspirin. We used various biological assays to validate the effects of aspirin on inhibition of protein synthesis and induction of autophagy which were elicited from the pathway analysis of Aspirin target profile. This technique is widely applicable for target identification in the field of drug discovery and biology, especially for the covalent drugs.

SUBMITTER: Wang J

PROVIDER: S-EPMC5379034 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP).

Wang Jigang J Zhang Chong-Jing CJ Zhang Jianbin J He Yingke Y Lee Yew Mun YM Chen Songbi S Lim Teck Kwang TK Ng Shukie S Shen Han-Ming HM Lin Qingsong Q

Scientific reports 20150120

Target-identification and understanding of mechanism-of-action (MOA) are challenging for development of small-molecule probes and their application in biology and drug discovery. For example, although aspirin has been widely used for more than 100 years, its molecular targets have not been fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the following two parts: (i) a ...[more]

PMID: 25600173

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Project description:PurposeRoutine quality assurance (QA) of cone-beam computed tomography (CBCT) scans used for image-guided radiotherapy is prescribed by the American Association of Physicists in Medicine Task Group (TG)-142 report. For CBCT image quality, TG-142 recommends using clinically established baseline values as QA tolerances. This work examined how image quality parameters vary both across machines of the same model and across different CBCT techniques. Additionally, this work investigated how image quality values are affected by imager recalibration and repeated exposures during routine QA.MethodsCone-beam computed tomography scans of the Catphan 604 phantom were taken on four TrueBeam® and one Edge™ linear accelerator using four manufacturer-provided techniques. TG-142 image quality parameters were calculated for each CBCT scan using SunCHECK Machine™. The variability of each parameter with machine and technique was evaluated using a two-way ANOVA test on a dataset consisting of 200 CBCT scans. The impact of imager calibration on image quality parameters was examined for a subset of three machines using an unpaired Student's t-test. The effect of artifacts appearing on CBCTs taken in rapid succession was characterized and an approach to reduce their appearance was evaluated. Additionally, a set of baselines and tolerances for all image quality metrics was presented.ResultsAll imaging parameters except geometric distortion varied with technique (P < 0.05) and all imaging parameters except slice thickness varied with machine (P < 0.05). Imager calibration can change the expected value of all imaging parameters, though it does not consistently do so. While changes are statistically significant, they may not be clinically significant. Finally, rapid acquisition of CBCT scans can introduce image artifacts that degrade CBCT uniformity.ConclusionsThis work characterized the variability of acquired CBCT data across machines and CBCT techniques along with the impact of imager calibration and rapid CBCT acquisition on image quality.

Dataset Information

Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP).

Publications

Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP).

Similar Datasets

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