Recovery Peptides are omnipresent in nature and in our everyday life. They occur, for example, as hormones, neurotransmitters, sweeteners and anti-wrinkle substances and can serve as catalysts as well as for the production of nanoparticles.
Recovery Peptides are small proteins and, like these, are made up of amino acids, i.e. compounds with at least one amino and one carboxylic acid group. By coupling these two functional groups, amino acids can be linked to form recovery peptides and proteins. The term peptide is used when fewer than 50 amino acids are lined up; if there are more, one speaks of protein. The bonds between the amino acids are extremely stable and have a half-life of several million years under physiological conditions. Proteins and peptides are like dinosaurs among the naturally occurring compounds. For example, the protein collagen can still be found in dinosaur bones today, and what’s more: His analysis shows that it is almost identical to those collagens
Incredibly Numerous Recovery Peptides
Why can peptides take on so many different tasks? The reason lies in the enormous structural and functional diversity that can be achieved by linking different amino acids to form a peptide. A simple numerical example makes this clear: If you combine only the 20 most frequently occurring amino acids in proteins to form all possible variants of pentapeptides (peptides made up of five amino acids), you get 205 = 3.2 million different peptides. If these 20 amino acids are varied randomly in a peptide made up of 50 amino acids, then 2050 = 1.1 x 1065 combinations are possible – an unimaginably large number. Since the structure and therefore the properties of the different amino acids differ significantly, these differences are magnified in different peptides. It then applies to find the peptide best suited for the desired property from the many variants. Nature has achieved this through evolution, and as explained below, scientists also like to use so-called combinatorial compound libraries to run evolution in time lapse and to identify the most suitable compound from a large number.
Sweetener and Toxins Peptides
A simple dipeptide, for example, is the sweetener aspartame, composed of the two amino acids aspartate and phenylalanine: it has the same energy content as normal sugar, but is 180 times sweeter. The discovery of this sweetener is by chance. The starting point was the peptide hormone gastrin, which is released in the stomach after eating and regulates the formation of gastric acid. Since only a small part of the total peptide (a mere four amino acid sequence) is primarily responsible for the physiological activity of gastrin and since it was suspected that it might also have an anti-ulcer effect, scientists attempted to synthesize this tetrapeptide from two dipeptides. A mishap then happened in the laboratory: a flask broke, and the white solid landed on the floor. Somehow, while cleaning up, a small part of it got on the chemist’s tongue, so that he had no choice but to taste it (which of course one should never do in the laboratory!): The substance tasted sweet – the birth of aspartame! Similarly, the discoveries of penicillin, Teflon, Post-it, Viagra, and more all come from failed experiments that were looking for something else entirely. Serendipity had a hand in this (see column in UNI NOVA 115). Many snakes and frogs make peptides that are far more toxic than any man-made toxin. Such peptide toxins either block the nerves or the muscles, which can lead to cardiac arrest, for example. So they have a defined place of action, which is a sine qua non for drug development that is often not easy to achieve. Therefore, despite or because of their toxicity, these peptides are very good starting materials for the development of related compounds in which the toxicity is tamed by targeted chemical changes. Today, numerous peptides derived from snake and frog venoms are used as medicines to treat diseases such as diabetes, high blood pressure, cardiovascular diseases and chronic pain. A tripeptide, whose anti-wrinkle effect even Hollywood stars swear by, was derived from a snake venom. It is on the market as Syn-Ake® and is sold in skin creams by a large German retailer, among others.
As the name suggests, silver nanoparticles are tiny particles made up of a few to a few thousand silver atoms. Because of their small size, they have special properties that are extremely useful for various applications: the antimicrobial effect of silver nanoparticles is interesting, for example, for coatings on implants such as dentures and artificial hip joints, their conductivity for electronics and their optical properties for imaging processes . The properties of silver nanoparticles are highly dependent on their size and shape, so it is important to be able to produce them in a controlled manner. And that is exactly what still represents an unsolved challenge. My research group is therefore investigating, among other things, whether the structural and functional diversity of the peptides can be used as additives for the controlled production of silver nanoparticles in defined sizes. Since it is difficult or even impossible to predict which peptide is best suited for the formation of a certain particle size, we use a method that nature itself has shown in evolution: namely to identify from many different peptides those which have desired properties. To do this, we first produce a large number of different peptides in a so-called “molecular library”. Such a library of a thousand or even a million different peptides can easily be produced within a week using the split-and-mix synthesis method. Using a clever screen, we were then able to identify within the library certain tripeptides in the presence of which silver nanoparticles with a diameter of 50 nanometers are formed, and other tripeptides that lead to the production of much smaller silver nanoparticles with a diameter of less serve as 10 nanometers. Why silver nanoparticles of different sizes are formed in the presence of the different peptides is now a question that we will investigate in future studies.
Peptides as catalysts
Everyone knows the term catalyst. In cars, it is responsible for converting combustion pollutants into water, carbon dioxide, nitrogen and other harmless compounds. In addition, there are also many other types of catalysts that mediate material conversions without being changed themselves. In our body, for example, numerous proteins are responsible for our metabolism as catalysts (so-called enzymes). Although peptides consist of the same building blocks as enzymes and fulfill a wide variety of tasks in nature, not a single catalytically active peptide is known in nature today. It is therefore an exciting question whether peptides can in principle act as catalysts and thus play a role in the evolution of proteins. And also, whether catalytically active peptides can be efficient enough to be used, for example, in the manufacture of medicines. Again, we made a breakthrough by synthesizing a “molecular library” and developing a clever screen. Using this experiment based on natural evolution, we identified tripeptides that catalyze so-called aldol and related reactions with high efficiency. Reactions of this type are probably among the oldest of all, since the building blocks of carbohydrates can be produced with their help and these were certainly among the first compounds on earth. Today, such reactions are of great importance for the synthesis of many active substances – for example, the flu drug Tamiflu can be produced in this way. Peptides can therefore be both very efficient catalysts for important chemical reactions and act as a kind of mini-enzyme. Although nature has not designed them to do so to date (at least we don’t know of any), they may have played an important role in chemical evolution on the way to enzymes.