Screening by Mass Spectrometry

Mass spectrometry (MS) has become an important tool for high-throughput screening, owing to its ability to directly probe interactions between target proteins and ligands from the libraries of drug-like molecules. Screening by mass spectrometry, both covalent and non-covalent, includes several approaches with different areas of application. To address a growing demand of our drug discovery partners, MS-based Screening group has been established at Bienta in 2019.

Being a part of Enamine, the largest manufacturer of screening compounds for drug discovery, Bienta has gained experience in covalent screening by MS. Among the variety of the covalent probes, Cysteine-specific binders are of the highest demand. Our MS-based screening group is working with a list of Cysteine covalent fragments and screening compounds libraries, as well as custom compound selections from specific Cysteine-targeted warheads, such as acrylamides, chloroacetamides, vinyl sulfone compounds, and others. The libraries are being constantly updated, to ensure a novel and diverse chemical space for the quests for new hits.

Our team is equipped with two Agilent Q-TOF LC-MS systems dedicated for MS screening projects. A typical covalent screening project consists of 2 stages: (1) method development and (2) the screening per se, including hit confirmation and counterscreen. We mostly work with the libraries in 384-well plate format.

For the data analysis, our software team developed an in-house data parser which goes through MS peak lists from individual wells, searching for protein-ligand conjugate peaks, and calculates % of adduct formation. To satisfy all customers’ requests and answer additional questions that may arise during the screening, our MS-based Screening group can perform a variety of hit follow-up services, including diverse orthogonal screens, intrinsic reactivity, kinetic studies, and ligand binding localization studies.

At Bienta, MS-based Screening group works in close collaboration with the Recombinant Protein Expression group. Target proteins can be produced in E.coli, baculovirus or mammalian systems.

For more details please contact us at and we will be happy to answer any of your questions.