Aspartyl-alanyl-diketopiperazine
Source Aspartyl-alanyl-diketopiperazine at Peptiology
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Summary
Aspartyl-alanyl-diketopiperazine (DA‑DKP) is a cyclic dipeptide fragment generated from the N‑terminus of human serum albumin during commercial preparation. Laboratory studies have shown that DA‑DKP can suppress activation‑induced cytokine release from human peripheral blood mononuclear cells and T‑lymphocytes, suggesting an immunomodulatory role. The compound is not an approved drug and has only been examined in vitro.
Mechanism of Action
DA‑DKP appears to act on activated T‑cells by increasing the active form of the small GTP‑binding protein Rap1. This elevation of Rap1 leads to reduced phosphorylation of downstream transcription factors ATF‑2 and c‑Jun, which are critical for the transcription of interferon‑γ and tumor necrosis factor‑α. The net effect is a dose‑dependent decrease in these pro‑inflammatory cytokines.
What the Research Shows
Two peer‑reviewed laboratory studies investigated DA‑DKP. The first quantified DA‑DKP (42–80 µM) in six commercial human serum albumin (HSA) products and demonstrated that both the HSA preparations and synthetic DA‑DKP inhibited interferon‑γ and TNF‑α release from activated peripheral blood mononuclear cells and a cloned T‑cell line in a dose‑dependent manner. The second study focused on the signaling pathway, showing that exposure of human T‑cells to DA‑DKP increased active Rap1 and concomitantly reduced phosphorylated ATF‑2 and c‑Jun, linking the peptide to T‑cell anergy. Both investigations were performed in vitro with human cells; no animal or clinical data were reported.
Reported Benefits
In vitro evidence indicates that DA‑DKP can dampen excessive T‑cell cytokine production, which could be valuable for controlling hyper‑inflammatory states such as sepsis or cytokine release syndromes. The peptide’s ability to modulate the Rap1‑ATF‑2/c‑Jun axis provides a mechanistic basis for potential immunosuppressive applications, although these benefits remain theoretical pending further research.
Limitations of the Evidence
All findings are limited to cell‑culture models; no animal studies, pharmacokinetic data, or human clinical trials have been reported. The concentrations used may not reflect achievable levels in vivo, and the relevance of DA‑DKP present in commercial albumin to therapeutic outcomes is unclear. Moreover, the compound’s stability, bioavailability, and off‑target effects have not been characterized.
Safety Considerations
No safety or toxicity data for isolated DA‑DKP are available. The studies only note that commercial HSA containing DA‑DKP can suppress immune responses, raising concern for immunocompromised patients receiving albumin infusions. Until formal safety assessments are performed, the peptide should be considered experimental, and any inadvertent exposure via albumin products warrants caution.
How It Is Administered
DA‑DKP has not been formulated as a standalone therapeutic. Research has employed synthetic DA‑DKP dissolved in aqueous media for cell‑culture experiments, and it has been detected as a contaminant in commercially prepared human serum albumin solutions administered intravenously. No specific dosage forms or routes beyond these experimental contexts are described.
Routes of Administration
No administration routes recorded yet.
Goals & Uses
No goal associations recorded yet.
Contraindications
No contraindications recorded yet.
Adverse Effects
No adverse effects recorded yet.
Drug Interactions
No drug interactions recorded yet.
Population Constraints
No population constraints recorded yet.
Regulatory Status
No regulatory status recorded yet.
Evidence & Sources
- Journal ArticleLowBar-Or D, et al.2006-01-01T00:00:00.000000Z
- Journal ArticleLowShimonkevitz R, et al.2008-01-01T00:00:00.000000Z
Frequently Asked Questions
What is Aspartyl‑alanyl‑diketopiperazine?
DA‑DKP is a cyclic dipeptide formed when the N‑terminal aspartyl‑alanyl segment of human serum albumin cyclizes during commercial albumin processing. It is present in all tested albumin preparations at micromolar concentrations.
Has DA‑DKP been approved for medical use?
No. The compound is not an approved drug; it has only been studied in vitro as a component of albumin solutions and as a synthetic molecule in laboratory experiments.
Could DA‑DKP be useful for treating inflammatory conditions?
Laboratory data show that DA‑DKP can reduce interferon‑γ and TNF‑α production by activated T‑cells, suggesting potential anti‑inflammatory effects. However, these findings are limited to cell cultures, and no in‑vivo or clinical evidence exists.
Are there any known risks associated with DA‑DKP?
Safety data are lacking. The only reported concern is that albumin products containing DA‑DKP may suppress immune function, which could be problematic for immunocompromised patients. Formal toxicity studies have not been published.
How is DA‑DKP administered in research studies?
In the cited studies, synthetic DA‑DKP was added directly to cell‑culture media at micromolar concentrations. It has also been identified in commercial human serum albumin solutions given intravenously, but it is not delivered as a separate medication.