Technology

At Insingulo, we believe that the best way to study the protein targets that are essential in many diseases, is to study the targets in their natural form. Our guiding principle is to deliver technology that is flexible enough to accommodate even the most difficult targets in their natural state. With other methods, it is necessary to manipulate and change these targets to adapt to the assay which reduces the viability of the results.

The context

Not only can our technology accommodate targets in their native state, but it can also detect single binding events. This allows you to measure the kinetics of screening compounds completely free from labels that can impede natural interactions.

Our technology gives you the flexibility to investigate your targets in a natural state, giving you data
that you can rely on. Our technology is validated in screening for membrane proteins, intrinsically
disordered proteins, PPIs, fragments, and much more.

Membrane proteins have an essential role in regulating physiological processes making them a prime target for therapeutic drugs in many different diseases. However, the most common methods for studying proteins can often not be used with membrane proteins which are much more challenging to work with due to their transmembrane domains. InSingulo presents a new and simple way to investigate membrane proteins as drug targets, unlocking new opportunities in drug discovery.

The challenge of membrane proteins

In order to accurately understand membrane proteins, they must be studied in their native environment, embedded in the cell membrane. Almost all methods used to study proteins for drug discovery require that proteins are removed from the membrane, which means that it is impossible to accurately understand how they will respond to drugs. Some methods allow membrane proteins to be reconstituted in artificial membranes which is an improvement, but can also deliver misleading results.

The InSingulo solution

Our propriety solution allows us to study the interaction of proteins bound in their native cell membranes with single molecule sensitivity. The InSingulo assay not only delivers accurate binding information without the need for labels, but it also does this in a dynamic way, delivering kinetic information in a single assay.

In essence, InSingulo combines the advantages of assays that conserve the biological context of a target, with the advantages of label-free biosensing.

- Tim Kaminski, Chief Scientific Officer

The Benefits of the InSingulo Technology

Conserves nature

Our assay can measure the interactions of membrane proteins while they are still embedded in their native membranes. Moreover, the preparation of these proteins is very simple. This is in stark contrast to the preparation of assay systems that attempt to mimic cell membranes, but lack the complexity to give real world data.

High specificity

The InSingulo method offers high specificity. Using our method, the membrane protein embedded in a vesicle remains free in solution and the target definition compound (TDC) is bound to the surface. Subsequently, test compounds can be introduced to screen them for their impact on the binding of the target to the TDC. Non-specific binding of ligands to the membrane or target does not affect the measurements making the InSingulo method highly specific.

High sensitivity

Single binding events, as detected by InSingulos technology, are the smallest increment of a binding
reaction, making our technology highly sensitive. Another advantage of InSingulo’s technology is that the signal levels are independent of the test compounds molecular weight.

Low reagent constraints

In contrast to other inhibition in solution assays, InSingulo’s technology allows using the use of
target definition compounds (TDC) with a broad affinity range from sub-nanomolar to micromolar.
Another difference with InSingulo’s technology is is that as a result of its single-molecule resolution,
the observed kinetics of the test compounds are not influenced by the binding kinetics of the TDC.

Free from this limitation, the same TDC can be used throughout the entire development process from screening to end of lead optimization.

The technology is applicable to soluble and membrane proteins. For membrane proteins, the technology is well suited to handle a huge variety of samples giving the scientists the freedom they need.

Applications

Where our technology provides you with a significant advantage

Membrane proteins

Membrane proteins represent the majority of drug targets. We have developed a process that simplifies the development process and increases the chances for success.

Intrinsically Disordered Proteins

Intrinsically disordered proteins (IDPs) are relevant in many diseases. They can occupy a variety of different conformations making them challenging to study.

Fragment screening

Fragment screening is a powerful method for identifying chemical starting points and developing them into small molecules therapeutics.