Kinase Inhibitor Pulldown Assay Identifies a Chemotherapy Response Signature in Triple-negative Breast Cancer Based on Purine-binding Proteins.

Unlabelled: Triple-negative breast cancer (TNBC) constitutes 10%-15% of all breast tumors. The current standard of care is multiagent chemotherapy, which is effective in only a subset of patients. The original objective of this study was to deploy a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) to identify kinases elevated in non-pCR (pathologic complete response) cases for therapeutic targeting.

Kinome Reprogramming Is a Targetable Vulnerability in ESR1 Fusion-Driven Breast Cancer.

Unlabelled: Transcriptionally active ESR1 fusions (ESR1-TAF) are a potent cause of breast cancer endocrine therapy (ET) resistance. ESR1-TAFs are not directly druggable because the C-terminal estrogen/anti-estrogen-binding domain is replaced with translocated in-frame partner gene sequences that confer constitutive transactivation. To discover alternative treatments, a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) was deployed to identify druggable kinases that are upregulated by diverse ESR1-TAFs.

A Transferable, Sample-Independent Calibration Procedure for Trapped Ion Mobility Spectrometry (TIMS).

Ion mobility spectrometry-mass spectrometry (IMS-MS) determines momentum transfer cross sections of ions to elucidate their structures. Recent IMS methods employ electrodynamic fields or nonstationary buffer gases to separate ions. These methods require a calibration procedure to determine ion mobilities from the experimental data.

Molecular Structures and Momentum Transfer Cross Sections: The Influence of the Analyte Charge Distribution.

Structure elucidation by ion mobility spectrometry-mass spectrometry methods is based on the comparison of an experimentally measured momentum transfer cross-section to cross-sections calculated for model structures. Thus, it is imperative that the calculated cross-section must be accurate. However, it is not fully understood how important it is to accurately model the charge distribution of an analyte ion when calculating momentum transfer cross-sections.

Steady-state asymmetric nanospray dual ion source for accurate mass determination within a chromatographic separation.

Here we report the design, implementation, and initial use of an asymmetric steady-state continuous dual-nanospray ion source. This new source design consists of two independently controlled and continuously operating nanospray interfaces with funnel shaped counter electrodes. A steady-state ion mixing region combines the ions from the two sources into a single ion beam in the intermediate region after ion extraction from the nanospray sources but before the bulk of the pressure gradient of the vacuum interface.