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This piece is republished from RebelBio’s cohort IV company, Valanx Biotech’s Medium .

Whether it be the sweeping eagle in his flight, or the open apple-blossom, the toiling work-horse, the blithe swan, the branching oak, the winding stream at its base, the drifting clouds, over all the coursing sun, form ever follows function, and this is the law.

Louis Sullivan, 1896


Architect Louis Sullivan looked at the animated world evident around him and concluded: Form follows function. Much has happened since 1896. We are now able to probe much deeper into the inner workings of life. What we find is, that Sullivans statement holds true, even for the most basic molecular work-horses we know: proteins.

Proteins are long strands made up of the 20 natural amino acids that are universal to every cell. Whether you are a tiny bacterium, that tries to make a living off of hot volcanoes thousands of feet below the sea or a human: Both use the same 20 amino acids to make up their proteins to keep their cells alive and thriving.

Proteins do everything. Even though they are strands and therefore rather two-dimensional in nature, they are able to fold into three-dimensional structures. It’s like tying a knot in a shoe string – the two-dimensional string gets a three-dimensional shape and a function – in the case of the shoestring keeping your shoes from falling off your feet.

The form that proteins so take then determines their function. Some of them do chemical reactions in your body, like the ones who help you to convert sugar into energy – those are called enzymes. Others are able to recognize and bind to invading bacteria and viruses thus alerting your immune system – these are called antibodies. The image below shows the three-dimensional structure of an enzyme and an antibody. Again, form follows function: There are distinct areas responsible for the proteins function.

Would it surprise you if I told you that these two proteins are responsible for a global market worth around 100 billion dollars? The sugar-converting enzyme is used in glucose biosensors which help millions of diabetes patients to monitor their blood sugar levels and thus manage their illness and live normal lives. Antibodies are used as drugs that help against cancer, autoimmune diseases and of course infectious diseases.

Proteins are amazing. But they could be even more amazing. Antibodies that can recognize and bind to cancer show immense promise as a delivery helper for chemotherapeutic drugs. This would mean that the toxic drugs responsible for the awful side effects in chemotherapy would be delivered directly to the cancer, thus eliminating the side effects of chemotherapy. Similarly, biosensors could be used not only to easily measure blood sugar levels but everything from environmental toxins in your home to the drug levels on your bloodstream; informing you when to take your next treatment for optimal medication impact and safety.

There is a reason why the development of these amazing protein products isn’t happening as fast as we would like to see it. Proteins have an inherent flaw. They are really difficult to attach things to in a controlled manner. Enzymes need to be attached to a surface, so that we can measure what they are detecting. And if we want to haul drugs specifically only to cancerous tissue they must be attached strongly to the antibody to avoid damage elsewhere in the body.

Form follows function. That means that there are areas on a protein that we shouldn’t meddle with because they are important for function. We are therefore forced to attach things to proteins at defined sites where the attachment doesn’t impair function. But we are not able to do that.

Until now.

The reason why we are not good at connecting things to proteins without disturbing their function is easily explained: Every protein usually contains more than one copy of each amino acid. To make a connection with a protein, we do a chemical reaction with specific amino acids, to be more exact specific chemical groups on the amino acid. Below is a picture of the chemical structures of the 20 amino acids found in nature. The green circles mark the chemical groups we can make connections with. We are pretty good at just targeting one TYPE of these amino acids.

But since there are multiple copies of one amino acid on a protein, we get connections to the protein everywhere. Below is a picture of a protein structure. One of the amino acids (lysine, for the science buffs) is shown in pink.

If we now do a chemical reaction that is specific for this amino acid, we end up with a mixture of proteins, where different copies of the amino acid did the reaction. In case of a reaction with a surface we end up with a jumbled landscape of proteins, connected in all kinds of different orientations. Some orientations kill the proteins activity and utility. In the case of connection with drugs, we end up with a mixture of different proteins where we neither know the site of the connection or the number. This is also shown below.

As stated above, this is a significant problem, hampering development of better products and drugs that could potentially improve people`s lives significantly.
We solve this problem quite simply by expanding nature`s toolset. We introduce a 21st amino acid. We produce this amino acid synthetically, meaning that this amino acid is not found in nature, but is entirely man-made. This amino acid can be placed anywhere in the protein. This allows us to choose where the connection with the protein is going to be, choosing a perfect site where function is not disturbed in the slightest.

What follows is the possibility to generate surfaces where the protein is precisely oriented as well as defined protein drugs where we know the site and the number of drugs attached.

Form follows function. Using our technology, we can use information about a proteins form to preserve its function in a very elegant way. This lets the protein do whatever it does best – whether it be chemical reactions or detecting cancer, viruses and bacteria.

Check out the RebelBio Cohort 4 Demo Day landing page here! Be on the lookout for the Demo Day live stream from London on July 26!

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