Are you struggling to characterize challenging binding events because of the limitations of your current biophysical method?


Monolith is the perfect solution to study interactions that involve ternary complexes, or targets only available at low concentration or small volume, as well as ones that aren’t suited for immobilization. And, other difficult situations.

Finally, characterize membrane proteins

Membrane proteins are notoriously difficult targets for traditional biophysical tools — optimizing buffer conditions takes a lot of work if you want to get an adequate amount of folded and functional protein needed for biophysical characterization with methods like SPR and ITC.

Here’s how Monolith helps if your biophysical method has failed to characterize molecular interactions involving membrane proteins.

What makes membrane proteins challenging?

How Monolith overcomes these issues

Native conformation is difficult to preserve if immobilized to a biosensor

Characterize them in solution – purified or from crude cell lysates. Or in nanodiscs, liposomes to preserve their conformation

Present low expression levels, so you typically don’t have enough for all your assays

Use only a tiny amount of protein sample

Must be isolated using detergents that cause issues with some biophysical assays

Measure their molecular interactions in any buffers, even with detergents and DMSO


Now evaluate Intrinsically Disordered Proteins (IDPs)

Because IDPs don’t fold into a homogeneous three-dimensional (3D) structure, their biophysical characterization is very challenging. They frequently engage in non-native intermolecular interactions that result in protein aggregation. Biophysical methods like SPR require immobilization and ITC requires high protein concentrations.

Here’s how Monolith resolves the limitations these methods present for the characterization of binding events with IDPs.

What makes IDPs challenging?

How Monolith overcomes these issues

Immobilization to a solid surface changes their conformational equilibrium

Measure in solution and at low protein concentrations

High protein concentrations required by some methods increase aggregation

Measure in solution and at low protein concentrations

Most methods fail to differentiate between binding and aggregation

Differentiate interactions between monomers, dimers, and larger fibrils

Monolith measures binding affinities between a small molecule and α-synuclein in solution

Binding affinities between epigallocatechin gallate (EGCG) and α-synuclein were determined under assay conditions that favored the oligomeric (purple trace) or fibrilar (blue trace) forms of α-synuclein. Each data set is an average of three independent experiments. With modification from Wolff , M., et al. Sci Rep 6, 22829 (2016)

Monolith measures binding affinities between a small molecule and α-synuclein in solution.

Want to hear more about how Monolith helps you characterize IDPs?


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Simplify the characterization of proteolysis-targeting chimeras (PROTACs)

PROTACs have a huge therapeutic potential for tackling undruggable protein targets. As they start to populate pharmaceutical companies’ pipelines, there is an urgent need to find a biophysical method to efficiently evaluate the ternary complex formed by PROTACs, Ubiquitin/ligase, and target protein.

Monolith helps to solve common problems researchers faced when studying ternary interactions.

What makes PROTACs challenging?

How Monolith overcomes these issues

Equilibrium conditions for binary and ternary interactions are difficult to control, affecting the calculation of the cooperativity value

Measure binary and ternary interactions and calculate the cooperativity value in solution under carefully controlled equilibrium conditions

Most biophysical methods require extensive assay development

Simplify assay development using only one fluorophore to characterize all components of the ternary complex

Learn how Monolith helps you facilitate the rational design of your PROTACs

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Your RNA-based therapeutics challenges are over

RNA molecules are involved in many cellular processes that cause disease and as a result, are becoming a new class of drug targets. Scientists are applying high-throughput screening and rational design approaches to identify ligands — small molecules, fragments, enzymes, etc. — that impact RNA cellular functions.

There are a few things Monolith does to help with your RNA therapeutics research.

What makes RNA therapeutics challenging?

How Monolith overcomes these issues

RNase-free environment is difficult to achieve in systems that include fluidics, e.g. SPR

Fluidics-free measurements, no special cleaning or flushing protocol to follow

RNA is inherently prone to degradation

Measurements take only a few minutes, so it’s easy to maintain the integrity of your RNA

It’s difficult to isolate enough intact RNA

Use only a few microliters per measurement


Working with DNA-encoded libraries?

What if you could expand the chemical space of your compound library by screening millions, billions, and even trillions of chemical compounds in a single, simple experiment? DNA-encoded libraries (DEL) let you do that thanks to a DNA tag that encodes the identity of each component in the library. After hits are identified from an initial screening process, they need to be confirmed using affinity-based biophysical methods.

With Monolith, this confirmation step can be automated, and done in solution with a small amount of sample. Take advantage of Monolith’s ability to measure a broad range of affinities from pM to mM.

Monolith helps identify a potent inhibitor of an epigenetic regulator from a DEL hit screen

Measurement of the molecular interaction between BAY-850 (a hit from a DEL screen) and ATAD2 (epigenetic regulator). BAY-850 inhibits the binding of ATAD2 to chromatin. Kd = 85 nM. From Fernández-Montalván, M. et al., ACS Chem. Biol. 12, 2730 (2017).

Monolith helps identify a potent inhibitor of an epigenetic regulator from a DEL hit screen.

Want to learn more about Monolith?

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