Pinealon: Molecular Structure

Molecular Structure and Properties#

Pinealon is a peptide whose molecular structure and properties have been characterized through analytical chemistry and structural biology studies.

Amino Acid Sequence#

Pinealon (EDR) is an ultrashort neuroactive peptide composed of three amino acids with the sequence Glu–Asp–Arg. The name “Pinealon” is used interchangeably with “EDR peptide” in the literature. Multiple reviews and experimental studies consistently identify EDR/Pinealon as a tripeptide and discuss its neuroprotective activity.

Molecular composition and mass. Recent tabulations list EDR (Glu–Asp–Arg) with the gross molecular formula C15H26N6O8 and an average molecular weight of 418.40 Da for the neutral peptide without counterion; the peptide is commonly supplied as an acetate salt. These reports focus on the peptide molecule and counterion rather than terminal modifications, and no terminal capping is indicated.

Isoelectric point and charge properties. Using the sequence and assuming free termini (consistent with reports listing the acetate salt but no capping), the ionizable groups are: N-terminus (pKa ~8.0), C-terminus (pKa ~3.1), Asp side chain (pKa ~3.9), Glu side chain (pKa ~4.2), Arg side chain (pKa ~12.5). From these, the isoelectric point is expected between the acidic side-chain pKa values, ~4.0–4.1. At physiological pH (~7.4) the peptide bears a net negative charge due to deprotonated Glu, Asp, and the C-terminus, with a localized positive charge on the C‑terminal Arg; the N-terminus is largely unprotonated at pH 7.4. Overall net charge at pH 7.4 is thus moderately negative (about −1 to −1.2). This distribution—basic Arg at the C-terminus opposed by acidic residues and a terminal carboxyl—also underlies the modeled DNA-binding orientation of EDR in the minor groove.

Structural features. As a three-residue peptide enriched in charged/polar side chains, Pinealon is expected to be highly hydrophilic and largely disordered/flexible in aqueous solution. Molecular docking and modeling studies place the positively charged C-terminal Arg toward the DNA minor groove; EDR and the related tripeptide KED show opposite orientations but similar placement of charged and polar groups in complexes with DNA, consistent with Arg/Lys side-chain placement driving binding. No experimentally determined 3D structure has been reported for EDR; studies describe it as a short, nuclear-penetrant, DNA/histone-interacting peptide.

Embedded summary table with key properties is provided below.

Stability and Formulation#

We identified Pinealon as the tripeptide Glu–Asp–Arg (EDR), extensively studied for neuroprotective activity in Khavinson’s short‑peptide literature. However, across the retrieved EDR papers (2017–2024), none reported experimental pharmaceutical stability data (solution pH stability ranges, temperature sensitivity, degradation kinetics, or labeled shelf‑life), nor formulation or storage specifications. These sources focus on biology and mechanisms, not CMC properties.

What is known about Pinealon stability:

• Primary EDR/Pinealon literature (Khavinson et al. 2017–2024) describes biological activity and mechanisms but reports no experimental pharmaceutical stability data (pH stability ranges, temperature sensitivity, shelf-life, degradation kinetics) or formulation/storage specifics.
• Plausible aqueous degradation pathways for a small acidic/arginyl tripeptide (Glu-Asp-Arg): backbone hydrolysis at peptide bonds; enzymatic proteolysis by peptidases; oxidation of Arg side chain and other residues by reactive oxygen species; deamidation/side-chain modifications and possible terminal modifications (sequence-dependent).
• Practical formulation considerations (general small-peptide principles, not EDR-specific data): lyophilization is preferred for long-term storage; avoid extreme pH (especially high pH which accelerates base-catalyzed hydrolysis); for aqueous use consider acetate/citrate buffers ~pH 4–6; include antioxidants and metal chelators if oxidation/metal-catalyzed degradation is a concern; protect from light and oxygen; use low-binding materials and single-use vials to reduce adsorption and freeze/thaw cycles.
• Recommended storage guidance (inferred from peptide best practices, not measured for Pinealon): keep aqueous solutions refrigerated (2–8 °C) and minimize time at room/elevated temperature; store lyophilized product at ≤−20 °C (preferably −80 °C for long-term) until reconstitution.
• Summary: No Pinealon-specific experimental stability results were found in the retrieved EDR papers; the above degradation pathways and formulation recommendations are reasoned inferences from peptide chemistry and should be validated experimentally for EDR/Pinealon.

Blockquote: Concise blockquote stating that Pinealon (EDR) primary papers contain no experimental stability data, listing likely degradation pathways and peptide formulation/storage best practices as reasoned inferences; useful as a starting-point for experimental stability testing.

Implications and best‑practice guidance by category

• pH stability: No direct EDR data found. Given the peptide’s acidic N‑terminal residues and a basic Arg at the C‑terminus, base‑catalyzed backbone hydrolysis would be expected to accelerate above neutral pH, with relatively greater stability anticipated in mildly acidic buffers; none of the EDR studies provides measured pH–rate profiles.
• Temperature sensitivity: No direct EDR data found. The biology papers imply aqueous handling and in vivo use but do not disclose storage or stress temperatures. As with other ultrashort peptides, hydrolysis and oxidation typically accelerate with heat; refrigerated solutions and frozen lyophilizates are standard precautions, not demonstrated for EDR in these sources.
• Degradation pathways: Not experimentally defined for EDR in the retrieved set. Plausible routes for Glu–Asp–Arg include backbone hydrolysis, enzymatic proteolysis, oxidation of arginine side chain by reactive oxygen species, and miscellaneous side‑chain/terminal modifications; these are inferred from peptide chemistry rather than reported measurements in the EDR papers.
• Formulation considerations: None of the EDR papers details buffers, pH targets, excipients, or lyophilization cycles. General small‑peptide practice would favor lyophilization for long‑term stability; use of acetate or citrate buffers around pH 4–6 to limit base‑catalyzed hydrolysis; minimizing oxygen and light; inclusion of antioxidants/metal chelators if oxidation is a concern; low‑binding containers and single‑use vials to reduce adsorption and avoid freeze–thaw; and cold‑chain storage (solutions 2–8 °C; lyophilizates ≤−20 °C). These recommendations are extrapolated and should be validated experimentally for EDR.

Conclusion Within the available EDR/Pinealon literature screened here, stability data specific to pH, temperature, degradation pathways, and formulation are not reported. The blockquote summarizes what is known and the best‑practice inferences. Targeted CMC studies (pH–rate profiling, isothermal and accelerated stability of solution and lyophilizate, forced‑degradation mapping, and excipient screening) are needed to establish Pinealon’s stability profile.

Pharmacokinetics#

We sought primary pharmacokinetic measurements for Pinealon (EDR; Glu‑Asp‑Arg) covering absorption, distribution, metabolism, elimination, half‑life, and bioavailability. Despite multilingual searches including synonyms, no peer‑reviewed studies were found that report quantitative ADME parameters for Pinealon (e.g., plasma half‑life, absolute oral bioavailability, tissue concentrations, BBB penetration measured in vivo, or defined metabolic/elimination pathways). Instead, available literature provides mechanistic context for ultrashort di‑/tripeptides that plausibly extends to EDR, but without Pinealon‑specific PK values.

Absorption and cellular transport. Di‑ and tripeptides are taken up across the small‑intestinal epithelium predominantly by proton‑coupled oligopeptide transporter PEPT1, a well‑characterized pathway that enables oral absorption of many small peptides and peptide‑mimetic drugs. Related transporters (PEPT2, PHT1, PHT2) mediate uptake/reuptake in other epithelia. Reviews also discuss that certain di‑/tripeptides can interact with LAT transporters (notably LAT1), suggesting potential facilitation of cellular entry in various tissues. These data imply that Pinealon, as a tripeptide, could be absorbed orally via PEPT1 and handled by PEPT family transporters in tissues; however, Pinealon‑specific uptake kinetics or bioavailability have not been measured in the retrieved literature.

Distribution and BBB penetration. LAT1 is expressed at the blood–brain barrier and transports neutral amino acids and some small peptides/drugs, motivating the hypothesis that ultrashort peptides might access the CNS via LAT carriers. Nevertheless, the reviewed sources provide no direct in vivo measurements showing Pinealon levels in brain or quantitative BBB permeability; thus, BBB penetration for Pinealon remains unquantified based on the evidence retrieved.

Metabolism and elimination. For small peptides, presystemic and systemic peptidases commonly cleave peptides to amino acids; renal handling via PEPT2 may reabsorb filtered peptides, with ultimate elimination of amino‑acid products primarily in urine. The mechanistic review notes these general pathways but does not delineate Pinealon’s metabolic products or measured excretion fractions, so Pinealon‑specific metabolism and elimination remain unreported.

Half‑life and bioavailability. No study located reported Pinealon’s plasma or tissue half‑life after any route, nor absolute oral bioavailability. Therefore, these parameters cannot be provided from current evidence identified here.

Conclusion. Current peer‑reviewed literature retrieved here offers mechanism‑based expectations for Pinealon’s absorption and handling via peptide and amino‑acid transporters but does not provide Pinealon‑specific pharmacokinetic measurements. Definitive values for absorption extent, tissue distribution (including BBB), metabolism, elimination routes and rates, half‑life, and oral bioavailability were not found in the sources identified.

Related Reading#

• Pinealon overview and research guide
• Peptides similar to Pinealon
• Pinealon research evidence