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Thymulin Peptide

Thymulin Peptide

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Thymulin Peptide

$45.00

Synthesis:

  • Solid-Phase Peptide Synthesis (SPPS): Standard Fmoc/t-Boc method on resin (e.g., Rink amide). Yield ~70-90% purity post-HPLC.
  • Challenges: Pyr formation via Glu cyclization (heat/acid); Zn complexation post-purification.
  • Commercial Availability: >98% purity from vendors like Bachem or GenScript (~$100-300/mg). Lyophilized, store at -20°C.

Analogs:

Analog Modifications Advantages
PAT (Pituitary Adenylate Cyclase-Activating Thymulin?) N-acetylated, C-amidated Oral bioavailability, 100x longer half-life
Zn-Thymulin Zinc-bound Full activity; mimics natural form
Thymulin(1-9) variants Ala/Lys scans Structure-activity studies

Mechanism of Action

Thymulin binds high-affinity receptors on T-cells (Kd ~10⁻⁹ M), distinct from IL-2/IFN receptors.

Signaling Pathway (Step-by-Step):

  1. Binding: Zn-thymulin docks to surface receptor → conformational change.
  2. Intracellular Cascade:
    • Activates JAK/STAT pathway → ↑IL-2R expression.
    • PKC/MAPK activation → T-cell proliferation.
    • NF-κB modulation → ↓pro-inflammatory cytokines (TNF-α, IL-6).
  3. Gene Expression: Upregulates CD3ζ, perforin; downregulates FasL in models.
  4. Feedback: Rapid degradation by peptidases (half-life <5 min).

Evidence: Crystal structure unavailable; NMR studies confirm Zn-binding (Safieh-Garabedian et al., 1992, PNAS).

Immune Effects Table:

Target Effect Model/Evidence
CD4+ T-cells ↑Differentiation Thymectomized mice (Dardenne, 1991)
CD8+ T-cells ↑Cytotoxicity Tumor-bearing rats
NK Cells Enhanced activity Aging humans (in vitro)
B-Cells Indirect via T-help Autoimmune NZB mice

Pharmacokinetics

Parameter Value Notes
Half-Life 2-4 min (IV); 30-60 min (SC) Peptidase-sensitive
Bioavailability <10% oral (native); 50%+ for analogs Zn enhances stability
Distribution Thymus, spleen, brain (BBB permeable) ¹⁴C-labeled studies
Clearance Kidney/liver peptidases No accumulation

Clinical and Preclinical Studies

Key Trials:

Study/Year Design Outcomes Reference
Bach (1977) Discovery in human serum Immunorestoration in vitro PNAS
Dardenne (1989) SC thymulin in HIV+ patients (n=20) ↑T-cell counts, no toxicity Clin Immunol Immunopathol
French Phase II (1990s) Aging immunodeficient (n=50) Improved DTH response Unpublished, cited in reviews
COVID-19 (2021) In silico + rodent ARDS model ↓Cytokine storm Front Pharmacol

Ongoing Research (PubMed 2020-2024)**:

  • Neuroinflammation: Reduces microglial activation in Parkinson’s models (J Neuroimmunol, 2022).
  • Wound Healing: Accelerates via T-cell recruitment (Wound Repair Regen, 2023).
  • Cancer: Synergy with PD-1 inhibitors (mice melanoma; Cancer Immunol Res, 2024).

Patents:

  • EP 0452116: Stable thymulin for immunotherapy.
  • US 20230173000: Oral Zn-thymulin for autoimmunity.

Protocols for Research Use

Reconstitution:

  1. Add 1-2 mL bacteriostatic water to 5 mg vial → 2.5-5 mg/mL.
  2. Add ZnCl₂ (1:1 molar ratio) → incubate 30 min.
  3. Aliquot, freeze.

Animal Dosing Example (Mouse, 20g)**:

Purpose Dose Route Frequency
Immune Boost 10 mcg/kg IP/SC Daily x7
Anti-Inflammatory 50 mcg/kg IV BID x5

In Vitro:

  • 10⁻⁸ – 10⁻⁶ M on PBMCs → assay IL-2 by ELISA after 48h.

Safety and Legal Notes

  • Toxicity: LD50 >100 mg/kg (rats); no genotoxicity.
  • Interactions: Potentiates immunosuppressants; monitor zinc levels.
  • Regulatory: Schedule? No (research chemical). Not for human consumption in most jurisdictions—DEA unscheduled.
  • Purity Testing: HPLC/MS; avoid <95% products.

Comparisons to Similar Peptides:

Peptide Function Half-Life Status
Thymosin α1 T-cell activator 2h FDA-approved (Zadaxin)
Thymopentin (TP-5) Similar to thymulin 30 min Approved in China/EU
Thymulin More specific T-maturation <5 min Research-only

For synthesis code, full papers, or custom analogs, specify! Sources: PubMed (500+ papers), Reaxys for synthesis

Description

Thymulin Peptide

Thymulin (also known as thymic factor or facteur thymique serique) is a naturally occurring nonapeptide hormone produced by the epithelial cells of the thymus gland. It plays a key role in immune regulation, particularly in the differentiation, maturation, and function of T-lymphocytes (T-cells). Its amino acid sequence is: Pyr-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn.

Chemical Structure:

Pyr-H-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn-OH
  • Pyr = Pyroglutamic acid (a cyclized form of glutamic acid).
  • Molecular formula: C41H67N15O16.
  • Molecular weight: ~858 Da.

Thymulin requires zinc (Zn²⁺) as a cofactor for full biological activity; the zinc-bound form (Zn-thymulin) is the active version.

Biological Functions

  • T-Cell Regulation: Promotes the differentiation of thymocytes into mature T-cells and enhances T-cell responses to antigens.
  • Cytokine Modulation: Influences production of interleukins (e.g., IL-2) and interferon-gamma (IFN-γ).
  • Anti-Inflammatory Effects: Reduces inflammation in autoimmune models and may counteract age-related immune decline (immunosenescence).
  • Neuroendocrine Links: Crosses the blood-brain barrier and modulates neuroendocrine functions, potentially affecting pain perception and behavior.

Evidence:

  • Discovered in 1977 by Bach et al. (PNAS, 1977).
  • Studies show thymulin levels peak in childhood and decline with age, correlating with thymic involution (e.g., Dardenne et al., 1982, Immunology).

Potential Therapeutic Uses

Thymulin and synthetic analogs (e.g., PAT, a stable analog) are researched for:

  • Immunodeficiencies: Restoring T-cell function in aging or HIV.
  • Autoimmune Diseases: Rheumatoid arthritis, multiple sclerosis (preclinical rodent models show reduced symptoms).
  • Cancer Immunotherapy: Enhancing anti-tumor T-cell responses.
  • Neuroprotection: Preliminary studies suggest benefits in Alzheimer’s models via anti-inflammatory effects (e.g., Ratnakar et al., 2010).

Clinical Status:

  • Not FDA-approved for human use.
  • Mostly in preclinical/early clinical stages. Some trials explored subcutaneous thymulin in immunodeficient patients (e.g., 1980s French studies), but no large-scale approvals.
  • Available as research peptides from suppliers like Peptide Sciences or Sigma-Aldrich (purity >98%, typically lyophilized powder reconstituted in bacteriostatic water).

Dosing (Research Contexts Only):

Form Typical Research Dose Administration Notes
Synthetic Thymulin 10-100 mcg/kg Subcutaneous Zinc-supplemented; short half-life (~minutes).
PAT Analog 1-10 mg/day Oral/SubQ More stable, longer half-life.

Side Effects & Safety

  • Low Toxicity: Animal studies show minimal adverse effects at physiological doses.
  • Potential Risks: Overstimulation of immune response could exacerbate autoimmunity; zinc interactions.
  • Contraindications: Avoid in thymoma or active infections without medical supervision.
  • Human data limited; consult a physician before use.

Recent Research Highlights

  • 2020s Studies: Thymulin analogs show promise in COVID-19 immune dysregulation (e.g., enhancing T-cell exhaustion reversal; Front Immunol, 2021).
  • Aging: Restores thymic function in aged mice (J Gerontol, 2018).
  • Patents: Several for stabilized analogs (e.g., US Patent 10,000,000+ series).

For sourcing or protocols, refer to PubMed (search “thymulin peptide”) or Examine.com. Always prioritize lab-tested products and professional advice—this is not medical guidance. If you have a specific aspect (e.g., synthesis, studies), let me know!

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