Services

We specialize in high throughput affinity selection mass spectrometry (ASMS) screens using the Automated Ligand Identification System (ALIS) on an Agilent 2D-HPLC system interfaced to an Agilent Time-of-Flight MS.

ASMS offers several distinct advantages over legacy high throughput screening (HTS) methods:

• ASMS is binding site agnostic, enabling clients to identify potential leads acting through a variety of mechanisms, including degradation and disruption of protein-protein or protein-oligonucleotide interactions.
• ASMS is compatible with a range of targets. Protein, RNA, and Protein Complexes can be screened without the need for tagging or surface immobilization, ensuring the results are physiologically relevant.
• ASMS requires very little target (~1mg) to screen hundreds of thousands of potential compounds.
• ASMS assay development is limited to buffer optimization and therefore much faster than traditional biochemical HTS methods like FRET and enzymatic assays, enabling identification of leads in half the time.
• ASMS is much faster to run than other biophysical assays such as SPR, interferometry, DSF, Mesoscale, ITC, and NMR.
• ASMS allows compounds to be screened in pools of 250: 100,000 test compounds can be screened in a single day.
• ASMS covers broad chemical space as positive mode electrospray ionization is compatible with 95% of drug-like test compounds.
• ASMS is immune to false positives resulting from active impurities and breakdown products by identifying the exact compound based on molecular formula.

We have extensive experience using ASMS screens to study hundreds of targets tested against tens of millions of compounds.

We can our in-house library, third-party libraries, and internal client libraries. While we typically screen Rule of Five compliant chemical libraries, we can also screen macrocyclics. We offer target QC on proteins and RNA to ensure accurate screens.

Following ASMS primary, pooled screens:

• We recommend clients run a secondary screen to confirm hits in small pools of one to five compounds.
• We can also rank order hits by competitive binding, give quantitative information on target occupancy, and determine binding affinity for Structure-Activity Relationship (SAR) studies.

Next day data delivery may be possible with couriered samples to our Billerica location.

Targeting the covalent modification of proteins with compounds containing reactive functional groups has led to the development of several new potent and selective drugs. Though historically covalent compound discovery has been conducted via structure guided design, direct covalent ligand screening of electrophilic compound libraries has gained popularity as a primary approach. Momentum has integrated mass spec hardware and software into an automated workflow that enables the primary screening of electrophilic libraries at a rate of 5,000 compounds daily. Additionally, the generation of “hit” lists from these screens has increased the demands on secondary assays defining and rank ordering compound potency. With minor modifications to plate prep protocols, Momentum can determine compound potency parameters, apparent Kinact /Ki.

We offer ICP-MS analysis for several applications depending on the needs of our clients’ specific programs. We have used ICP-MS to test for trace metals in CGT and biologics media, perform pharmacokinetic studies on metallodrugs, quantify biomarkers for rare diseases (Ex. Wilson’s Disease), and characterize zinc finger proteins.

• We understand that ICP-MS results are crucial to go-forward decision making in CGT and biologics development, so we strive to turn around data as fast as possible. We can analyze hundreds of samples daily.

Next day data delivery may be possible with couriered samples to our Billerica location.

Momentum offers assay development and analysis for small molecule quantification on both HPLC-MS and RapidFire-MS. The RapidFire-MS system allows ultrafast, automated, label-free functional screening. We provide functional cell-based and biochemical screening generating 20,000 datapoints per day and up to 80,000 using BLAZE-mode. These analyses are often a follow-up or related experiments to our screening research. We can perform biomarker quantification, potency assays, and pharmacokinetic studies. We have extensive experience measuring lipids, amino acids, sugars, and metabolites. Momentum has limited to no lead time, efficient methodologies, and extensive LCMS experience meaning results are delivered in days to weeks, instead of months.

Small Molecule Analysis Assays

• Biomarker validation and screening from cell culture, biological fluids, or tissue
• Functional assay design and development for rare diseases
• Potency assays
• Small molecule library QC

We provide functional cell-based and biochemical screening, and have the capacity to generate upwards of 20,000 datapoints per day.

• As the inventors of the RapidFire-MS platform, we have 20 years of experience in RapidFire analytical method development and biochemical assay development.

Next day data delivery may be possible with couriered samples to our Billerica location.

Momentum has extensive experience in the analysis of oligos by mass spectrometry enabling 6 service types with industry leading turn-around time. Our assays leverage high-throughput sample preparation, multiple dedicated high-resolution LCMS instruments, and automated data analysis software allowing the measurement of over 5,000 samples a day. We routinely work with RNA/DNA oligos that are heavily modified and/or > 100 nucleotides in length.

Services at a glance

• Mass determination
• Purity analysis
• Impurities analysis
• Covalent modification
• RNA cap and tail analyses
• Sequencing

Instrumentation

• TOF and QTOF mass spectrometers
• LC and RapidFire High-throughput Systems

Momentum specializes in the discovery and development of reversible and covalent small molecule binders. The core proteomics services we offer are an extension of our covalent ligand screening and ASMS screening assays – answering questions downstream of finding hits.

Following covalent ligand discovery, Momentum’s proteomic assays can determine the site and occupancy of compound modification on the protein. Activity based protein profiling can be used to identify on- and off-target interactions in vivo on a proteome-wide scale.

Following the identification of reversible small molecule binders by the ASMS assay, Momentum’s proteomic assays can, for examples, measure their effect on splicing, post translational modifications, or targeted protein degradation.

Together, Momentum’s deep expertise in screening assays and quantitative multiplexed proteomics allows our clients to progress from target of interest to compounds with cellular activity in just a few months.

Services at a glance

• Protein mass and purity analysis
• Protein identification
• Sequence confirmation
• Covalent modification mapping
• Covalent protein binding in vivo (ABPP)
• Global quantitative profiling in vivo
• Kinase profiling in vivo
• PTM analysis in vivo

Instrumentation

• Orbitrap Ascend, QTOF, and QQQ mass spectrometers
• Extensive automation for sample preparation