Splenopentin
Splenopentin (SP-5) is a spleen-derived immunomodulatory pentapeptide (Arg-Lys-Glu-Val-Tyr) structurally analogous to thymopentin (TP-5) that modulates both T-cell and B-cell immune responses, with research applications in immunomodulation and comparison studies with thymic peptides.
Splenopentin (SP-5) is a synthetic pentapeptide corresponding to the active site sequence Arg-Lys-Glu-Val-Tyr, derived from a spleen-associated immunoregulatory protein. It is the structural analog of thymopentin (TP-5, Arg-Lys-Asp-Val-Tyr), with a single amino acid substitution at position 3 (glutamic acid replacing aspartic acid).
Overview
Splenopentin emerged from research in the 1980s exploring immunoactive peptides derived from organs other than the thymus. While the thymus had yielded a rich family of immunomodulatory peptides (thymosin alpha-1, thymopentin, thymulin), researchers hypothesized that the spleen — as a major secondary lymphoid organ — might produce its own immunoregulatory peptides. Splenopentin was identified as a pentapeptide sequence from splenic tissue with immunomodulatory activity analogous to, but distinct from, the thymic peptide thymopentin.
The key structural difference between splenopentin (Arg-Lys-Glu-Val-Tyr) and thymopentin (Arg-Lys-Asp-Val-Tyr) is a single amino acid substitution: glutamic acid (Glu) in position 3 replaces aspartic acid (Asp). Both are acidic amino acids, differing by a single methylene group (-CH₂-), yet this substitution influences receptor binding affinity and downstream signaling, resulting in subtly different immunological profiles.
Splenopentin research has been primarily preclinical, with studies conducted in murine and in vitro models. While it has not achieved the clinical development of thymopentin or thymosin alpha-1, it has contributed to understanding the broader landscape of immunomodulatory peptides and the role of the spleen in immune regulation.
Mechanism of Action
T-Cell Differentiation: Like thymopentin, splenopentin promotes the differentiation of immature T-cell precursors, inducing expression of T-cell surface markers. Audhya et al. (1987) demonstrated that SP-5 induces T-cell differentiation in vitro, although with somewhat different kinetics and potency compared to TP-5.
B-Cell Modulation: The most distinctive feature of splenopentin relative to thymopentin is its enhanced effect on B-cell function. SP-5 promotes B-cell proliferation and immunoglobulin production, particularly IgM and IgG synthesis. This B-cell activity is consistent with the peptide's splenic origin, as the spleen is a major site of B-cell activation and antibody production.
Cytokine Modulation: Splenopentin modulates cytokine production by both T cells and macrophages. It enhances IL-2 and interferon-gamma production (supporting cell-mediated immunity) while also promoting IL-4 and IL-6 production (supporting humoral immunity), reflecting its dual T-cell/B-cell modulatory profile.
Macrophage Activation: SP-5 enhances macrophage phagocytic activity and antigen-presenting function. Singh et al. (1998) demonstrated that splenopentin increases macrophage respiratory burst activity and enhances clearance of bacterial pathogens in animal models.
Reconstitution Calculator
Splenopentin
**Splenopentin** (SP-5) is a synthetic pentapeptide corresponding to the active
Set up a clean workspace with all supplies ready.
7x / week for weeks
Research
Immune Modulation
The foundational research on splenopentin established its immunomodulatory properties. Audhya et al. (1987) characterized SP-5 as a pentapeptide with T-cell differentiating activity analogous to thymopentin but with additional B-cell modulatory effects. The study demonstrated that SP-5 induces Thy-1 antigen expression on murine pre-T cells and enhances plaque-forming cell responses (a measure of B-cell antibody production).
Spangelo et al. (1987) further characterized the immunological properties of splenopentin, showing that it enhances both mitogen-induced lymphocyte proliferation and natural killer cell activity. The peptide demonstrated dose-dependent effects with optimal activity in the nanomolar range.
Comparison with Thymopentin
Comparative studies have been central to splenopentin research. Goldstein et al. (1987) directly compared SP-5 and TP-5 in multiple immunological assays, finding that while both peptides promote T-cell differentiation, SP-5 has superior B-cell stimulatory activity. TP-5 was more potent in T-cell-specific assays, consistent with its thymic origin.
The single amino acid difference (Glu vs Asp at position 3) was shown to affect receptor binding characteristics. Structure-activity relationship studies indicated that the additional methylene group in glutamic acid alters the peptide's charge distribution and receptor interactions, shifting the balance of immunological activity toward B-cell modulation.
Limited Clinical Development
Despite promising preclinical results, splenopentin has not advanced through clinical trials to the extent of thymopentin or thymosin alpha-1. Several factors have contributed to this limited development:
- Thymopentin (TP-5) was already in advanced clinical development for similar indications
- The single amino acid substitution made it difficult to justify a separate development program
- The spleen-derived origin did not confer a clear clinical advantage over thymic peptides
- The short half-life (typical of small peptides) posed formulation challenges
Research interest has continued at a preclinical level, particularly in understanding how subtle structural differences between related immunomodulatory peptides influence biological activity.
B-Cell Effects
Splenopentin's enhanced B-cell activity has been studied in the context of humoral immune responses. Research demonstrated that SP-5 enhances polyclonal B-cell activation, promotes immunoglobulin class switching, and increases antibody affinity maturation. These effects are consistent with the spleen's role as the primary organ for T-cell-dependent B-cell responses and antibody production.
Singh et al. (1998) showed that splenopentin administration in immunosuppressed mice restored both cellular and humoral immune parameters, including splenic plaque-forming cell responses and delayed-type hypersensitivity reactions.
Safety Profile
Based on preclinical studies, splenopentin demonstrates a favorable safety profile:
- Systemic toxicity: No significant toxicity observed at immunomodulatory doses in animal studies
- Immunological: Immunomodulatory rather than immunosuppressive; does not cause broad immune suppression
- Short half-life: Rapid clearance limits risk of sustained adverse effects
- Limited human data: No clinical trials have reported safety data in humans
- Theoretical concerns: As with all immunomodulatory agents, caution warranted in autoimmune conditions and organ transplant recipients
Pharmacokinetic Profile
- Half-life
- Not formally established (~minutes, similar to TP-5)
Quick Start
- Route
- Subcutaneous, intravenous (research)
Molecular Structure
- Formula
- C₂₈H₄₇N₇O₉
- Weight
- 693.8 Da
- CAS
- 105184-37-0
- PubChem CID
- 121827
- Exact Mass
- 693.3810 Da
- LogP
- -6
- TPSA
- 328 Ų
- H-Bond Donors
- 11
- H-Bond Acceptors
- 12
- Rotatable Bonds
- 23
- Complexity
- 1130
Identifiers (SMILES, InChI)
InChI=1S/C31H51N9O9/c1-17(2)25(29(47)39-23(30(48)49)16-18-8-10-19(41)11-9-18)40-28(46)22(12-13-24(42)43)38-27(45)21(7-3-4-14-32)37-26(44)20(33)6-5-15-36-31(34)35/h8-11,17,20-23,25,41H,3-7,12-16,32-33H2,1-2H3,(H,37,44)(H,38,45)(H,39,47)(H,40,46)(H,42,43)(H,48,49)(H4,34,35,36)/t20-,21-,22-,23-,25-/m0/s1
DRCNRVYVCHHIJP-AQBORDMYSA-NResearch Protocols
subcutaneous Injection
Administered via subcutaneous injection.
intravenous Injection
Administered via intravenous injection.
Interactions
Peptide Interactions
| Property | Splenopentin (SP-5) | Thymopentin (TP-5) | |----------|---------------------|---------------------| | Sequence | Arg-Lys-Glu-Val-Tyr | Arg-Lys-Asp-Val-Tyr | | Source | Spleen | Thymus (thymopoietin 32-36) | | Position 3 | Glutamic acid | Aspartic acid | | B-cell effects | More pronou...
Quality Indicators
What to look for
- Well-established safety profile
- Multiple peer-reviewed studies available
Caution
- Limited human data available
- Short half-life may require frequent dosing
- Evidence primarily from preclinical studies
Red flags
- No clinical trials conducted
Frequently Asked Questions
References (5)
- [3]Goldstein G, Audhya TK Thymopoietin and splenin: chemistry, biology, and clinical applications Surv Immunol Res (1987)
- [1]Audhya T, Scheid MP, Goldstein G Contrasting biological activities of thymopoietin and splenin, two closely related polypeptide products of thymus and spleen Proc Natl Acad Sci USA (1987)
- [2]Spangelo BL, Hall NR, Goldstein AL Biology and chemistry of thymosin peptides Ann N Y Acad Sci (1987)
- [5]
- [4]Singh VK, Grupta S, Udupa KN Effect of splenopentin on immune response in mice Indian J Exp Biol (1998)
Somatropin (rHGH)
Somatropin is recombinant human growth hormone (rHGH), a 191-amino acid protein identical to endogenous pituitary-derived growth hormone. It is FDA-approved for growth hormone deficiency, Turner syndrome, and other conditions, and is widely studied for anti-aging, body composition, and tissue repair applications.
SS-31
SS-31 (elamipretide) is a mitochondria-targeted tetrapeptide that stabilizes cardiolipin to improve ATP production and reduce reactive oxygen species, with research applications in mitochondrial myopathy, heart failure, diabetes, and inflammatory diseases.