Services

Affinity Selection Mass Spectrometry (ASMS)

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.

Covalent Binding Assays (Protein & RNA)

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.

Inductively Coupled Plasma Mass Spectrometry (ICP-MS)

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.

Small Molecule Analysis

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

RapidFire-MS High Throughput Functional Assays

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.

Biomolecule Analysis

Momentum’s biomolecule analysis applications are an extension of our binding assay screens allowing our clients to further characterize their targets. Momentum offers quality control services on proteins and oligonucleotides using high-resolution MS platforms. Data delivery as fast as 2-4 business days after sample receipt at our Billerica, MA location.

Protein Analysis

We can work with purified protein or cell lysates to provide:
  • Protein identification
  • Protein mass determination
  • Protein purity determination
  • Protein sequence confirmation

Oligonucleotide Analysis

We can work on DNA/RNA samples with both standard and modified chemistries to provide:
  • Intact mass determination/confirmation on oligos > 100 nucleotides in length
  • Target purity
  • Component profiling
  • RNA cap and tail analyses
  • Sequence confirmation

Chemoproteomics

Chemoproteomics encompasses an array of methods used to identify and interrogate protein-small molecule interactions. Momentum’s chemoproteomic applications are an extension of our binding assay screens allowing our clients to further characterize their targets, hits and leads.

An example of the extension of services enabled by chemoproteomics is irreversible covalent binding analysis. Momentum has been offering a high-throughput intact mass shift assay to identify electrophilic test compounds that bind protein targets for several years. We can now help our clients characterize the binding site of the covalent adduct by doing peptide mapping. We can further characterize those test compounds in cellular assays showing on and off target binding in vivo.

We deliver chemoproteomics results by leveraging several mass spectrometers including QqQ, QTOF, and two Orbitrap Ascend Tribrid systems – equipped with nanoLC, extended mass range, ETD, and FAIMS capabilities. These instruments collectively produce high resolution MS data with speed, specificity, and sensitivity. To accelerate turnaround time, we also have several automation solutions for sample preparation including Integra, Tecan, AssayMAP Bravo, and AccelerOme.

Chemoproteomics Applications
  • On- and off-target covalent modification in vitro
  • On- and off-target covalent modification in vivo
  • On- and -off target covalent modification site specificity in vitro and in vivo
  • Targeted quantitative profiling
  • Global quantitative profiling

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