Thymosin Alpha-1

Thymosin Alpha-1 Peptide

Thymosin Alpha-1 is a naturally occurring 28-amino acid polypeptide first identified and isolated from the thymus gland in 1972. It is classified as an immunomodulatory agent due to its significant effects on the immune system. Following its discovery, Talpha1 has been the subject of extensive preclinical and clinical studies exploring its therapeutic potential across a diverse range of diseases, including chronic viral infections, various cancers, cystic fibrosis, and sepsis. Currently, Talpha1 is an approved medical therapy used to combat chronic hepatitis B and C infections in over 35 countries globally.

Thymosin Alpha-1 Peptide Overview

Thymosin Alpha-1 (Talpha1) is understood to mediate its biological activity primarily through its interaction with the immune system's command centers. Research suggests it binds to Toll-Like Receptors (TLRs), specifically those found on antigen-presenting cells (APCs) like dendritic cells. This binding action is theorized to be the mechanism that triggers the production and release of key signaling molecules known as cytokines, including Interleukin-2 (IL-2) and Interferon-gamma (IFN-gamma). These cytokines are vital components of the adaptive immune response, responsible for enhancing the maturation, proliferation, and cytotoxic function of T lymphocytes and Natural Killer (NK) cells.

Additionally, Talpha1 has been shown to improve the efficiency of antigen presentation by dendritic cells, which helps the immune system better recognize and respond to foreign invaders. Experimental data also supports the peptide's role in regulating the overall immune response by balancing the profile of pro-inflammatory and anti-inflammatory cytokines, promoting essential immune homeostasis.

Thymosin Alpha-1 Peptide Structure

Thymosin Alpha-1 is a linear 28-amino acid polypeptide. Its chemical composition is defined by the molecular formula C129H215N35O43. The amino acid sequence is highly conserved across multiple species, reflecting its foundational role in mammalian immunity.

Amino Acid Sequence: Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH

Molecular Weight: 3108.31 Da

IUPAC Name (Formula): N-[ (N-acetyl-L-seryl)-L-alpha-aspartyl-L-alanyl-L-alanyl-L-valyl-L-alpha-aspartyl-L-threonyl-L-seryl-L-seryl-L-alpha-glutamyl-L-isoleucyl-L-threonyl-L-threonyl-L-lysyl-L-alpha-aspartyl-L-leucyl-L-lysyl-L-alpha-glutamyl-L-lysyl-L-lysyl-L-alpha-glutamyl-L-valyl-L-valyl-L-alpha-glutamyl-L-alpha-glutamyl-L-alanyl-L-alpha-g1lutamyl]-L-asparagine

Thymosin Alpha-1 Research

Thymosin Alpha-1 and Its Role in Immune Modulation

The core function of Talpha1 is as a powerful modulator of immune activity, originating from the thymus gland, a primary site for the development and maturation of T-cells. T-cells are the foundational elements of the adaptive immune system, enabling the body to develop immunological memory and coordinate a specific, targeted response against pathogens.

In studies using animal models lacking a thymus (athymic mice), administration of Talpha1 was observed to partially restore immune function and protect against widespread infection. This demonstrates the peptide's ability to activate key signaling pathways and stimulate the secretion of immunoregulatory molecules that coordinate immune cell function.

Area of Research

Key Mechanisms and Findings

Potential Application

Hepatitis

Direct antiviral activity; potent immune enhancer to boost the effectiveness of Hepatitis B and C vaccines.

Approved therapy in many countries.

Sepsis

Helps regulate the excessive and destructive host immune response (cytokine storm) to infection.

Adjunctive therapy candidate for critical care.

Oncology

Exhibits anti-proliferative effects against cancer cells; used in conjunction with chemotherapy to enhance efficacy and survivability.

Component in research for cancer vaccines.

Fungal Infections

Promotes maturation of Dendritic Cells, improving their ability to recognize and present fungal antigens.

Adjunct therapy to traditional antifungals.

Neuroprotection

Enhances neurodevelopment and supports cognitive function; reduces inflammation in the central nervous system (CNS).

Research into neurodevelopmental disorders (e.g., cerebral palsy).

One promising application of Talpha1 is its use as a vaccine adjuvant. Inactivated vaccines are safe but often fail to elicit a strong, durable immune response. Talpha1 has been shown to enhance the immune response to these vaccines, potentially providing stronger and longer-lasting protection.

The peptide's role in modulating the immune response is also critical in the context of sepsis, a life-threatening syndrome characterized by a dysregulated, overly aggressive immune response to infection. Talpha1 may help prevent this destructive overreaction, thereby reducing organ damage and improving patient survival outcomes.

Thymosin Alpha-1 Encourages Neural Growth

Talpha1 research has highlighted the critical interplay between the immune system and the central nervous system (CNS). Studies have suggested that Talpha1 acts as a significant enhancer of neurodevelopment. Administering the peptide peripherally has been associated with improved cognitive performance in mouse models. The data indicates that Talpha1 influences genes involved in neuron growth and synaptic connection formation. Furthermore, it modifies the neural environment by supporting development while inhibiting pathways linked to inflammation and neuronal dysfunction. These findings suggest Talpha1 could be explored for research into various neurodevelopmental disorders.

Thymosin Alpha-1 and Fungal Infections

Dendritic cells (DCs) are sentinel immune cells vital for identifying and initiating a response against fungal pathogens. Talpha1 has been demonstrated to promote the maturation and activation of these dendritic cells, thereby strengthening the immune system's capacity to fight fungal pathogens. Research involving Aspergillus infections showed Talpha1 could activate T-helper cells, further boosting antifungal immunity. This has led to the exploration of Talpha1 as an adjunct therapy to improve the efficacy of standard antifungal treatments.

Thymosin Alpha-1 and Hepatitis

Talpha1 is an effective, accessible therapeutic option for chronic hepatitis B and C in many countries. Its benefits include both a potential direct antiviral effect and robust immune enhancement, making it valuable for use alongside vaccines to increase their protective efficacy.

Thymosin Alpha-1 and HIV

Despite successful suppression of the virus with antiretroviral therapy (ART), complete restoration of immune function often remains challenging for individuals with HIV, characterized by reduced cytotoxic T-cell activity and chronic inflammation. Studies suggest Talpha1 may help restore immune balance and improve the overall quality of life for individuals undergoing HAART. Talpha1 is theorized to activate CD8 T-cells, prompting the release of factors that help block HIV infection in other immune cells and prevent the reactivation of latent HIV reservoirs.

Thymosin Alpha-1 Research and Blood Pressure

Recent findings suggest that Talpha1 may act as an inhibitor of the Angiotensin-Converting Enzyme (ACE), a key enzyme in blood pressure regulation. By blocking ACE, Talpha1 could help lower blood pressure. This mechanism is comparable to that of common ACE-inhibiting drugs (like lisinopril) used for hypertension. However, Talpha1 may provide similar cardiovascular benefits—such as blood vessel relaxation, reduced cardiac remodeling, and improved kidney function—without the typical adverse side effects associated with synthetic ACE inhibitors.

Thymosin Alpha-1 Research and Cancer

Studies involving human lung cancer cells (A549) suggest that Talpha1 possesses anti-proliferative properties, slowing the growth and dissemination of tumor cells. The peptide also appears to limit cell migration, which is crucial for preventing metastasis. Furthermore, combining Talpha1 with the chemotherapy drug dacarbazine demonstrated improved progression-free survival in models without increasing toxicity, suggesting a synergistic effect. Researchers are also exploring Talpha1's potential in developing cancer vaccines due to its natural presence and strong immune-boosting effects.

A long-acting Talpha1 analogue was tested in mouse models of breast cancer and found to be even more effective at slowing tumor growth. It was observed to increase the counts of CD4 and CD8 T-cells and boost levels of immune signaling molecules like IFN-gamma and IL-2.

Talpha1 has been and continues to be actively studied for its potential in treating various cancers, including:

• Breast cancer
• Melanoma
• Liver cancer
• Lung cancer
• Colon cancer

Thymosin Alpha-1 Research and Inflammatory Pain

Given its established anti-inflammatory properties, Talpha1 is being researched as a potential therapeutic agent for inflammatory pain. Studies in mice indicate that Talpha1 can reduce pain perception by interfering with key pathways involved in inflammation. The peptide acts directly at the inflammation site to decrease the production of pro-inflammatory cytokines such as TNF-alpha and IL-1 beta. This mechanism offers a distinct approach to pain relief compared to conventional anti-inflammatory drugs.

Thymosin Alpha-1 and Cystic Fibrosis

A hallmark of Cystic Fibrosis (CF) is chronic inflammation and dysfunction of the CFTR protein. Research suggests that Talpha1 can reduce this persistent inflammation and may also enhance the proper functioning of the CFTR protein. These findings support Talpha1's potential as a single-agent therapeutic option for CF.

Damaged Teeth and Thymosin Alpha-1

Studies examining Talpha1 in models of avulsed (knocked-out) and replanted permanent teeth indicate that the peptide may assist in the healing of surrounding soft tissues and enhance the survival rate of the replanted tooth. These findings suggest Talpha1 could be beneficial in managing traumatic dental injuries, improving the prognosis for successful tooth restoration.

The Future of Thymosin Alpha-1

The extensive research into Talpha1 continues to unlock its diverse therapeutic potential, building upon its status as an approved medical therapy in multiple countries. Current research is focused on optimizing its delivery, enhancing its efficacy, and developing more cost-effective synthesis methods. Future clinical trials are highly anticipated for modified, long-acting versions of Talpha1 across a wide range of diseases. Talpha1 remains a highly promising agent for immune system regulation, consistently demonstrating low toxicity and minimal side effects in studies.

STORAGE

Storage Instructions

All products are prepared via lyophilization (freeze-drying), a process that ensures product stability for shipping, typically lasting 3–4 months.

Lyophilization, or cryodesiccation, is a specialized dehydration method involving freezing the peptide and then removing the water by sublimation (solid directly to gas) under low pressure. This results in a stable, white crystalline structure—the lyophilized peptide—which can be safely stored at room temperature until it is ready for reconstitution.

Once reconstituted with bacteriostatic water or another appropriate solvent, peptide solutions must be refrigerated to maintain efficacy. Most reconstituted solutions remain stable for up to 30 days when properly stored.

Best Practices For Storing Peptides

Correct storage protocols are essential for maintaining the integrity, stability, and reliability of laboratory research results. Adhering to these practices helps prevent contamination, oxidation, and degradation.

• Upon Receipt: Peptides should be stored in a cool, dark environment.
• Short-Term Storage (Days to Months): Refrigeration at or below 4 degrees C (39 degrees F) is appropriate. Lyophilized peptides generally maintain stability at room temperature for several weeks, which may be acceptable for short-term needs.
• Long-Term Storage (Months to Years): For optimal stability and to prevent structural changes over extended periods, peptides should be stored in a freezer at -80 degrees C (-112 degrees F).

Preventing Oxidation and Moisture Contamination

Protecting peptides from air and moisture is crucial for stability. Moisture contamination frequently occurs when a cold vial is opened. To prevent condensation from forming on the peptide or inside the container, always allow the vial to reach room temperature before opening it.

Minimize air exposure by keeping the container sealed as much as possible. After removing the required amount, promptly reseal the container. Storing the remaining peptide under a dry, inert gas atmosphere (such as argon or nitrogen) can further prevent oxidation. Peptides containing cysteine (C), methionine (M), or tryptophan (W) residues are particularly susceptible to air oxidation and require careful handling.

To preserve long-term stability, minimize freeze-thaw cycles. It is strongly recommended to divide the total peptide quantity into smaller aliquots, each intended for a single experiment. This limits repeated exposure to air and temperature fluctuations.

Storing Peptides In Solution

Peptide solutions have a significantly reduced shelf life compared to lyophilized forms and are prone to bacterial degradation. Peptides containing cysteine (Cys), methionine (Met), tryptophan (Trp), aspartic acid (Asp), glutamine (Gln), or N-terminal glutamic acid (Glu) residues degrade more rapidly in solution.

If storage in solution is necessary, use sterile buffers with a pH between 5 and 6. The solution should be aliquoted to minimize freeze-thaw cycles. Most peptide solutions remain stable under refrigeration at 4 degrees C (39 degrees F) for up to 30 days. However, less stable peptides should be frozen when not in immediate use.

Peptide Storage Containers

Storage containers must be clean, durable, chemically resistant, and appropriately sized to minimize air space. Both glass and plastic vials are acceptable. High-quality glass vials offer superior clarity, stability, and chemical inertness. Though peptides are often shipped in plastic to mitigate breakage, they can be safely transferred to glass or plastic based on specific research and storage needs.

Peptide Storage Guidelines: General Tips

Adhere to these best practices for maximum stability and integrity:

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize exposure to air to reduce oxidation.
• Protect peptides from light exposure.
• Do not store peptides in solution long term; keep them lyophilized whenever possible.
• Aliquot peptides based on experimental needs to prevent unnecessary handling.

Reference Citations

Garaci E, Pica F, Serafino A, et al. Thymosin al and cancer: action on immune effector and tumor target cells. Ann NY Acad Sci. 2012;1269:26-32. https://doi.org/10.1111/j.1749-6632.2012.06735.x

Romani L, Bistoni F, Gaziano R, et al. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103(11):4232-4239. https://doi.org/10.1182/blood-2003-09-3099

King R, Tuthill C. Immune modulation with thymosin alpha 1 treatment. Vitam Horm. 2016;102:151-178. https://doi.org/10.1016/bs.vh.2016. 04.007

Ciabattini A, Pettini E, Medaglini D. Thymosin alpha 1 as immune adjuvant in therapeutic vaccines. Expert Opin Biol Ther. 2018;18(sup1):61-67. https://doi.org/10.1080/14712598.2018.1518214

Sherman KE, Sjogren MH, Creager RL, et al. Thymosin al and interferon for chronic hepatitis C: a randomized, placebo-controlled trial. Hepatology. 1998;27(4):1128-1135. https://pubmed.ncbi.nlm.nih.gov/9537447/

Cordero OJ, Salgado FJ, Vinuela JE, et al. Immune activation by thymosin alpha 1 in subjects with immunodeficiency. Int Immunopharmacol. 2001;1(12):1949-1959. https://doi.org/10.1016/S1567-5769(01)00139-1

Costantini C, Bellet MM, Pariano M, et al. A reappraisal of thymosin al in cancer therapy. Front Oncol. 2019;9:873. https://doi.org/10.338 9/fonc.2019.00873

Matteucci C, Grelli S, De Smaele E, et al. Thymosin alpha 1 and immune response: new insights and potential applications. Future Sci OA. 2017;3(3):FSO236. https://doi.org/10.4155/fsoa-2016-0089

ClinicalTrials.gov. Thymosin Alpha 1 in Immunodeficiency. https://clinicaltrials.gov/ct2/show/NCT00586981

Fabris N, Garaci E. Thymosin alpha 1 in immunotherapy. Methods Find Exp Clin Pharmacol. 1991;13(3):167-176. https://pubmed.ncbi.nlm. nih.gov/1886031/