DSIP is a nine-residue peptide, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, isolated from rabbit blood in the mid-1970s by Monnier and Schoenenberger in Basel and named delta sleep-inducing peptide after the electroencephalogram band they were scoring. Unlike almost every other peptide in the research catalog, it has no identified gene, no precursor protein and no identified receptor, a gap that a 2006 review in the Journal of Neurochemistry called still unresolved. It is a chemically simple, highly polar nonapeptide with no cysteine, no methionine and no basic residue.
That combination — a well-defined molecule with an unsettled biology — is what makes DSIP unusual to work with. This profile covers its identity data, how it was isolated, what is and is not known about its target, a naming confusion that still appears in databases, and how the powder behaves in the laboratory.
DSIP at a glance
| Property | Value |
|---|---|
| Name | Delta sleep-inducing peptide (DSIP) |
| Sequence | Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE) |
| Length | 9 residues, free N-terminus, free C-terminal acid |
| Molecular formula | C35H48N10O15 |
| Molecular weight | 848.8 g/mol |
| CAS number | 62568-57-4 |
| PubChem CID | 68816 |
| International nonproprietary name | Emideltide |
| Gene / precursor | None identified |
| Receptor | None identified |
An international nonproprietary name is a naming decision, not an approval. Emideltide has no approved application with the FDA, and the compound is not an approved drug in the United States.
What the sequence contains, and what it lacks
For a peptide of its era, DSIP is a chemist's simple case. The composition explains most of its behavior in a vial.
| Feature | Consequence |
|---|---|
| One Trp (position 1) | The only strong chromophore; gives absorbance near 280 nm |
| Three Gly (positions 3, 4 and 8) | High backbone flexibility, little secondary structure |
| Asp5 and the C-terminal Glu | Net negative charge near neutral pH; a low isoelectric point |
| No Lys, Arg or His | No basic side chain to balance the two carboxylates |
| No Cys | No disulfide chemistry, no thiol oxidation, no scrambling |
| No Met | No thioether to oxidize |
| Free C-terminal acid | No amide to hydrolyze; one more negative charge than an amidated analog |
The practical summary is a small, acidic, unstructured peptide that dissolves readily in water and elutes early on a reversed-phase column. Nothing about the sequence resembles the melanocortins, the opioid peptides or the RF-amides; the 2006 review makes the same point, noting that the structure differs from any other known peptide family. Background on why a chain of this length is called a peptide at all is in what peptides are, and on the bonds themselves in the peptide bond.
How it was isolated
The work came out of Marcel Monnier's laboratory in Basel with Guido Schoenenberger, over a series of papers running through the 1970s. The group collected cerebral venous blood from rabbits, fractionated a dialysate of it, and tracked fractions by the electroencephalogram pattern they produced when infused into the brain ventricles of other rabbits. The tenth paper in that series, in Pflügers Archiv in 1977, reported the final isolation and characterization of the active nonapeptide.
The 1977 report in the Proceedings of the National Academy of Sciences gave the sequence and tested it against synthetic analogs. The authors synthesized the nonapeptide, five possible fragments (residues 1–8, 2–9, 2–8, 1–4 and 5–9), two nonapeptide analogs with two residues exchanged, and a related tripeptide, then infused all nine under double-blind conditions in 58 rabbits including controls, with cortical and archicortical leads analyzed by Fourier transform. The paper reports that only the full synthetic nonapeptide produced the delta and spindle electroencephalogram pattern the assay scored. A companion paper in Experientia compared the properties of the original isolate with the synthetic nonapeptide.
Those reports establish the molecule and the assay it was defined by. They do not establish a mechanism, and half a century later that is still the open question.
The biology that was never filled in
Most peptides in a research catalog can be traced to a gene, a precursor and a receptor. For DSIP, none of the three exists.
Kovalzon and Strekalova reviewed the field in 2006 under the title "Delta sleep-inducing peptide (DSIP): a still unresolved riddle". Their summary is blunt: the link between DSIP and sleep has never been further characterized, in part because of the lack of isolation of the DSIP gene, protein and possible related receptor, so the original hypothesis remains poorly documented. They also observe that DSIP-like immunoreactivity is distributed in neurosecretory hypothalamic nuclei of several vertebrate species in a pattern that does not match sleep regulation, and propose that a different, still unidentified DSIP-like peptide accounts for much of what antibody-based studies have detected.
Two consequences follow for anyone designing an experiment. First, there is no receptor assay for DSIP: no binding assay against a cloned target, no reference agonist or antagonist, and no standard cell line. Work with the peptide is therefore phenotypic or biochemical rather than receptor-pharmacological. Second, any assay that depends on an anti-DSIP antibody is measuring immunoreactivity, not the nonapeptide, unless the signal is confirmed by mass spectrometry.
A naming confusion worth knowing
Searching protein databases for "delta sleep-inducing peptide" returns a human protein, UniProt Q99576, listed under the alternative names "DSIP-immunoreactive peptide" and "delta sleep-inducing peptide immunoreactor". That entry is TSC22D3, also called glucocorticoid-induced leucine zipper (GILZ), a 134-residue intracellular protein in the TSC-22 family that acts on transcription factor activity in immune cells.
TSC22D3 is not a precursor of DSIP. Its sequence does not contain WAGGDASGE, and the alternative names are an artifact of the antibody-based screening that first labeled it. The lesson is the one Kovalzon and Strekalova drew: in this literature, "DSIP" sometimes names the nine-residue chemical and sometimes names whatever an antiserum bound, and the two are not interchangeable.
What the research literature covers
Because there is no receptor, the DSIP literature is a scattered set of biochemical and physiological reports rather than a pharmacological program. Published work falls broadly into three groups:
- Rodent and rabbit electroencephalogram studies, the original assay format, in which cortical frequency bands are scored after infusion into the brain ventricles or the bloodstream. The 2006 review notes that certain synthetic structural analogs of DSIP, rather than DSIP itself, produced the more reproducible slow-wave effect in the reviewers' own earlier work.
- Immunohistochemical mapping, using anti-DSIP antisera to locate immunoreactive material in hypothalamic and other nuclei across vertebrate species. This is the work that generated the DSIP-like-peptide hypothesis.
- In-vitro biochemistry, where the peptide is applied to tissue or cell preparations and enzyme activity or metabolite levels are measured. The review describes this spectrum of reported activity as broad and still unexplained.
A study design that takes the gap seriously usually includes a scrambled-sequence control, a mass-spectrometric identity check on the lot in hand, and a fragment such as DSIP(1–8) or DSIP(2–9) as a negative control, since those fragments were synthesized and tested in the original 1977 paper.
Regulatory status
DSIP is not an approved drug. No application containing it has been approved by the FDA, and it is not an ingredient in any approved product in the United States. The name emideltide exists because an international nonproprietary name was assigned, which happens during development and carries no marketing status.
Anhydrolabs supplies DSIP as a research reagent for in-vitro laboratory use, not for human or veterinary diagnosis, treatment, or consumption. The research use page sets out the terms of supply.
Handling DSIP in the laboratory
The compound arrives as a lyophilized powder in vacuum-sealed vials, and in 10-vial kits. Its composition makes it easier to handle than most peptides of comparable length.
- Solubility. With two carboxylates, no basic residue and three glycines, DSIP is strongly hydrophilic and normally dissolves in water without a co-solvent. A neutral or slightly basic buffer dissolves it as well; strongly acidic conditions are not needed.
- Solution stability. The main chemical liabilities are the aspartate, which can cyclize to an aspartimide under basic conditions and over time, and the serine hydroxyl. Storing stocks frozen in single-use aliquots at mildly acidic to neutral pH avoids both problems; how to reconstitute peptides covers the method.
- Storage of the powder. Sealed vials are kept cold, dry and dark, with −20 °C the usual long-term condition. Let a vial reach room temperature before opening so that moisture does not condense onto the solid. How to store peptides explains why that order matters.
- Concentration checks. Trp1 gives the peptide absorbance near 280 nm, which makes a spectrophotometric check of a stock straightforward against the nominal concentration, allowing for the water and counter-ion content stated on the certificate.
- Chromatography. A short, very polar peptide elutes early in a reversed-phase gradient, close to the void, so an ion-pairing agent and a shallow gradient are usually needed to separate it from salts and from deletion sequences.
- Identity. A monoisotopic mass measurement is the quickest identity check, and it also distinguishes the nonapeptide from the fragments used as controls, which differ by whole residues rather than by fractions of a dalton.
