QASciT - TB-500, a horse drug for doping

30 June 2011 - Racing cyclists use horse drug TB-500 for doping

What is TB-500?


TB-500 is the name used for a doping product, used up to now for horses in the hippic sport. It is different from most doping stuff while it is a peptide, a short protein with a few tens of amino acid beads on a string. It is derived from a natural compound, called thymosin beta 4, short TB-4, which is present all over our body for the control of the mechanics in the cells: it gives instructions to the work horse protein, called actin (from action) which builds scaffolds in the cell, moves around the numerous cell constituants, makes the muscles contract etc. TB-500 is a synthetic peptide, partly copied from TB-4; in this way it copies also the activities of TB-4 and thus interferes with the muscles. In this way it can influence the performance of horses and athletes.

Doping products

Amphetamine or benzedrine, a well known doping product (speed), which is very similar to the natural compound adrenaline; both are working on the nervous system

Dianabol, an anabolic steroid, belonging to another series of doping products, similar to cholesterol

Doping of athletes has been practised since antiquity. Usually plants or extracts of plants were used in order to improve the capacities of sportsmen. The body reacted to some constituents of these plants, which are now well-defined chemical substances. They are often the same drugs used by partygoers and addicted people.

Some people are constantly looking for new doping products , for two reasons, one, in order to find out if they can bring them to still better performances, two, while new products often are not on the black list of banned substances. One of the newer stuffs seems to be TB-500, which would be used for racehorses in Australia. Most doping drugs are complex molecules, which are composed in a very specific way but seldom with more than 50 atoms.

Cholesterol, remark the complex structure with three 6-rings and one 5-ring



Ammonia and acetic acid (the acid in vinegar) are bound together to form the base of amino acids. On the central carbon atom nature puts twenty different groups, which produces the series of 20 amino acids used in all living beings, from microbes to man

TB-500 belongs to another group; it is a small protein (small proteins are also called peptides). Proteins are one of the three classes of substances which the living world, man, animals, plants, microbes, is built with (you find them, next to the other categories carbohydrates and fats, on the information label of foods). Proteins are chains of smaller molecules, called amino acids; nature uses 20 different amino acids. A protein is like a necklace composed of beads of 20 different colours, located in whatever sequence.

Nature plays around with proteins to perform very different things in living beings; they are hormones, muscles, skin, hair, receptors, catalysts for the thousands of different reactions. Live is a very complex chemical factory which is largely run by proteins. The building blocks, these amino acids, are simple compounds: ammonia and acetic acid, both well-known in the household, are put together see figure), and on this combination nature places 20 different extensions of one, four up to 18 atoms. So all amino acids possess an amino group (from the ammonia) and an acid group. They can easily be fixed together like the beads on a necklace see figure). The sequence of the beads defines the specific properties of the protein. Sometimes the chain is formed by just a few amino-acids: only five in one of the endorphins, which are the proteins which give you the nice feeling after exertion, or far more, often a few hundred in receptors, catalysts etc, up to 34,350 in titin, the largest protein in the human body; it brings about elasticity in muscles. TB-500 is a synthetic protein, which means that the amino acids have been stringed together in a laboratory. In this synthesis the sequence of the beads is the same as in the central part of a natural protein, called TB-4, which is short for thymosin beta 4.




The two simplest amino acids, left glycine and right alanin (with just one carbon extra on the central carbon), are bound to form a dipeptide with release of a molecule of water. In this way nature produces thousands of different proteins with chains of just a few up to tens of thousands of amino acids

The thymosins are a group of small proteins (peptides), originally found in the thymus gland, but later detected all over the body. Beta thymosin is a subgroup and nr. 4 is one of them. TB-4 is a string of 44 amino acids. TB-500 is only part of TB-4; on the one hand it is simpler than the normal doping drugs while it is composed of simple building blocks; on the other hand it is more complex with 10 times more atoms. TB-4 regulates the operation of another, far bigger protein, called actin, which is responsible for the mechanics in the cell, at the inside for the construction of filaments and the motion of cell constituents, at the outside for the movement of the cell, for instance for the contraction of muscles. So it is not surprising that TB-500 can affect the performance of horses.

The synthesis of proteins is an expensive process. Therefore drug developers synthesise part of the original, test it and the best result is marketed. Such combinations can be very powerful: horses are injected with doses of only 10 mg of TB-500. One dose costs about 300 euro each, 30 euro per milligram, 30 million euro per kilogram, that is 1000 times more expensive than gold! It is clear that one has to be very careful with so powerful products, as they always will have also other effects in the body. TB-500 is not approved for human use, so nobody knows the outcome neither on the short-term nor on the long-term. 


Protein string of the natural product TB-4 (for the amateurs of puzzles):

MSDKPDMAEI EKFDKSKLKK TETQEKNPLP SKETIEQEKQ AGES, 4 groups of 10 amino acids plus 4; each letter indicates an amino acid (click here for the table of the amino acids); molecular weight 4921 dalton. Underneath the first 10 amino acids (MSDKPDMAEI) on the string.