Tymalin peptide (synthetic thymulin)
Tymalin peptide sequence: Pyr-L-Ala-L-Lys-L-Ser-L-Gln-Gly-Gly-L-Ser-L-Asn-OH
Research of thymalin
Thymalin is an immunomodulatory polypeptide obtained from the thymus gland. Synthetic thymulin (thymalin) is the main polypeptide consisting of 38 amino acid residues. Studies have shown that this immunomodulatory molecule is indeed found in the thymus. A brief summary of studies and conclusions concerning thymus functions is described below.
This is a specialized two-lobed secondary lymphoid organ that is crucial for the development of functionally active and self-deficient T-cells. It is also a component of the adaptive immune system. Research has shown that the actions of the thymus are mediated by immunomodulators.
In the thymus, thymocyte precursors develop into mature T cells. The maturation process includes the recombination and rearrangement of gene segments that code for the T-cell receptor. This leads to the development of unique peptide: MHC (major histocompatibility complex) receptor combinations, and this ensures central tolerance. These T-cell receptors provide antigen recognition and presentation antigen. Mediation occurs through interactions between antigen epitopes and corresponding paratopes of the T-cell receptor.
The process of gene rearrangement is prone to errors, which can lead to the development of either non-functional T cells or T cells that strongly react to autoantigens (autoreactive T cells). To prevent these errors, developing T cells are selected based on the affinity and specificity of their T cell receptors. Functional T cells are subjected to positive selection, and autoreactive T cells - negative selection. This occurs in the central medulla of each lobe of the thymus gland.
Mature T-cells eventually enter the general circulation, where they make up the repertoire of T-cells that mediate the functions of the adaptive immune system. Usually, the normal population of T-lymphocytes is reached at an early age, and this leads to involution of the thymus in early adulthood. DiGeorge, which is characterized by severe immunodeficiency. During adult life, final T-cell lymphopoiesis is still observed. However, studies have shown that complete involution of the thymus in old age is associated with increased susceptibility to severe infections and the development of cancer.
Other diseases associated with thymus dysfunction include allergic hypersensitivity, severe combined immunodeficiency syndrome (SCID), lymphomas, myasthenia gravis, thymomas, and rare APECAD (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy).
Thus, from studies conducted on the thymus gland, it is clear that the inductive environment provided by the thymus gland leads to the development of a functional, self-sufficient T-cell repertoire.
Thymus immunomodulators have the potential to restore the integrity of thymus activity in a dysfunctional or damaged thymus, which allows treating the associated immunodeficiency or regulating its severity. One of the most effective and efficient pharmaceutical preparations of thymus immunomodulators is thymalin.
How does timalin work
It is based on the principle that natural peptides have a significantly high potential to restore normal biological activity, and are also associated with an acceptable toxicological profile. Research has shown that biological activity is restored by the active component of the drug (polypeptide component), while the toxicological profile is usually associated with the carrier used.
In thymalin, the active component is a polypeptide, and the carrier used is a combination of water-soluble salts. Research has shown that the immunostimulating effects of thymalin are due to the ability of the polypeptide to modulate the ratio of subpopulations of functional immunocomponent cells.
Specific studies
The studies reviewed below are known to have provided convincing results, and as such, their results are relevant to the clinical use of thymalin as an immunomodulating agent.
- Thymalin and factor of the thymus gland.
One of the earliest studies of the immunomodulating potential of thymus derivatives was conducted in 1982 by Pisarev et al. In the study entitled "Isolation, physical, chemical and biological properties of an immunodeficiency polypeptide biomodulator from the thymus. extract, which was subjected to fractionation procedures to obtain three fractions designated 1, 2, and 3, which were then analyzed for immunobiological activity. The corresponding molecular weights and isoelectric potentials of the fractions were also measured. The tyrosine content in the fractions was also measured using the Lowry method. The results showed that fraction 1 did not show immunobiological activity. Fraction 2 and fraction 3 both showed immunobiological activity, and fraction 3 showed a more effective profile of immunostimulating activity. Fraction 3 was named thymalin and its conformational structure and properties were clarified. After that, it was introduced into the culture of lymphocytes obtained from pseudooperated and thymectomized guinea pigs. The results showed a significant increase in the population of lymphocytes obtained from thymectomized guinea pigs, while as there was no noticeable increase in the population of lymphocytes obtained from sham-operated guinea pigs. When the thymus factor was introduced into a similar culture,
- Tymalin and cervical cancer.
In 1984, Dexter conducted a clinical study called "Clinical and immunological changes in patients with cervical cancer after treatment with thymalin", the purpose of which was to evaluate the beneficial effect of thymalin on immunosuppressive conditions. In the study, 50 patients with cervical cancer were evaluated. These patients registered low levels of lymphocytes of varying degrees of severity before administration thymalin. After the introduction of thymalin, lymphocyte populations were measured, and it was found that they significantly increased in patients registering a normal or almost normal lymphocyte count. Thus, the results of this study demonstrate the need to include thymalin in cervical cancer treatment plans.
- Thymal hyperplasia and endometrium
In 1989, Zaporozhian et al. They conducted a study called "The influence of thymalin on immunological indicators and the morphofunctional structure of the uterus in guinea pigs with endometrial hyperplasia", the purpose of which was to evaluate the antitumor effects of thymalin. There were 125 female guinea pigs studied, and the endometrial hyperplasia was caused by the introduction of sinestrol. The parameter used to monitor the progress of the specified pathology was the population lymphocytes. This population decreased as the hyperplasia worsened. Introduction of thymalin to sick subjects led to the normalization of immune system parameters (that is, restoration of the lymphocyte population to the normal reference range) and partial restoration of the morphology of the endometrium.
Thus, from the above-mentioned three studies, it can be concluded that thymalin acts through the thymus, restoring both the quantitative and qualitative abilities of T-cell lymphocytes. This also shows that thymalin is being investigated for the potential treatment of various types of cancer.
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