DSIP is a nonapeptide, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, with free N- and C-termini, a molecular weight of 848.81 g/mol and two catalogue strengths, 5 and 10 mg. Its full name, delta sleep-inducing peptide, is unusual in a catalogue because it is a sentence about one experiment, carried out in rabbits in Basel in the 1970s, that reads as if it were a property of the vial.
This guide covers where the sequence came from, what the originating papers actually measured, why the later literature is mixed and says so, and the chemistry of the nine residues that matters to a buyer: an aspartate in the middle of a flexible chain, a tryptophan at one end, and what both mean for storage and for what a certificate re-test should look for.
| DSIP | Catalog specification |
|---|---|
| Vial strengths | 5 mg, 10 mg |
| Sequence | Nonapeptide Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu (WAGGDASGE) with free N- and C-termini; originally isolated from cerebral venous blood of sleeping rabbits (full sequence per COA). |
| Molecular formula | C35H48N10O15 |
| Molecular weight | 848.81 g/mol |
| Amino acid count | 9 |
| CAS number | 62568-57-4 |
From the Restate Health catalog record. Lot-specific values are on the certificate of analysis.
The 1977 isolation
Schoenenberger and Monnier, Proceedings of the National Academy of Sciences 1977, describe a peptide isolated from rabbits that produced delta-wave electroencephalogram enhancement after infusion into the brain ventricles. They named it delta-sleep-inducing peptide and gave its sequence as Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, the sequence the catalogue records. The source material, as the 2006 review by Kovalzon and Strekalova puts it, was rabbit cerebral venous blood, and the catalogue's own record says the peptide was originally isolated from the cerebral venous blood of sleeping rabbits.
The PNAS paper is also the first synthesis. The group made the nonapeptide, five fragments of it (residues 1-8, 2-9, 2-8, 1-4 and 5-9), two analogues with two residues exchanged and a related tripeptide, and infused all nine into the ventricles of rabbits under double-blind conditions, 58 animals including controls, with the EEG recorded from neocortex and archicortex and analysed by fast Fourier transform. Only the full synthetic nonapeptide enhanced the delta and spindle patterns. A companion paper in Pflugers Archiv the same year, the tenth in a series, reports the final isolation and characterisation, and a third in Experientia compares the original isolate with the synthetic peptide.
That is the experiment the name describes: a particular EEG readout, in rabbits, after infusion into the brain. It is a precise description of what was observed and a poor description of what a buyer should expect from a compound.
The name is a hypothesis, and the later literature says so
Kovalzon and Strekalova, Journal of Neurochemistry 2006, review the subsequent three decades under the title "a still unresolved riddle". Their summary is direct: the link between DSIP and sleep was never further characterised, in part because no DSIP gene, precursor protein or receptor has been isolated; the hypothesis of DSIP as a sleep factor is, in their words, extremely poorly documented and still weak; and the peptide's structure resembles no known peptide family. They note that DSIP-like immunoreactivity maps to hypothalamic neurosecretory nuclei that are not particularly involved in sleep regulation, and that in their own earlier rabbit and rat work certain structural analogues, but not DSIP itself, promoted slow-wave sleep. They propose that a DSIP-like peptide, not yet identified, may account for both the immunoreactivity and the activity.
| What the name implies | What the 1977 paper reports | What the 2006 review concludes |
|---|---|---|
| A peptide that induces sleep | Enhanced delta and spindle EEG patterns in rabbits after infusion into the brain ventricles | The sleep link was never further characterised; the hypothesis is weakly documented |
| A natural signalling molecule | Isolated from rabbit cerebral venous blood; sequence determined and confirmed by synthesis | No gene, precursor or receptor identified; natural occurrence remains obscure |
| A defined mechanism | Not addressed | Analogues, not DSIP itself, were active in the authors' own rabbit and rat studies |
The 1977 result is from Schoenenberger and Monnier (PNAS); the later assessment is from Kovalzon and Strekalova (2006).
For a buyer the conclusion is simple. The compound is a well-defined nonapeptide with a verifiable sequence and mass, and that is what a certificate can speak to. The name attached to it describes a 1977 observation that the field has not resolved, and nothing in the record or the literature supports reading it as a property. The material is supplied for laboratory research, where the open question is the reason to study it rather than a claim about it.
The sequence, read for chemistry
Nine residues, in one-letter code WAGGDASGE, with nothing modified at either end. PubChem records the compound as CID 68816 with the formula C35H48N10O15, a molecular weight of 848.8 g/mol and a monoisotopic mass of 848.33, filed under CAS 62568-57-4, the number in the catalogue record. The catalogue figure, 848.81, agrees. Note that at this size the average and monoisotopic masses differ by only half a dalton, so a certificate's observed mass should land within a dalton of either and the basis matters less than it does for a large peptide.
- One aromatic residue, tryptophan at position 1. It is the only chromophore at 280 nm, which makes ultraviolet quantification possible, and it is the residue in the chain most prone to oxidation.
- No cysteine and no methionine, so there is no disulfide to form or scramble and no thioether to oxidise.
- No asparagine or glutamine, so the classic deamidation route does not arise.
- One aspartate at position 5, between glycine at 4 and alanine at 6, and a glutamate at the C-terminus. Together with the free C-terminal carboxyl these make the peptide net negative at neutral pH, with the N-terminal amine as its only basic site.
- Two consecutive glycines at positions 3 and 4. Glycine has no side chain and gives the backbone unusual flexibility around that point.
An acidic peptide of this kind is generally soluble in water, and peptide solubility explained uses DSIP as its worked example of counting net charge. The item that needs the rest of this guide is the aspartate.
Asp5 and the residue after it: the isomerisation site
Aspartate in a flexible peptide can rearrange without any enzyme. The backbone nitrogen of the following residue attacks the aspartate side-chain carbonyl, closing a five-membered succinimide ring. That ring then hydrolyses in either of two directions, back to ordinary aspartate or to isoaspartate, in which the backbone now runs through what was the side chain. Some racemisation to the D-forms accompanies the process. Peptide degradation pathways covers the route alongside the others; this section is about how fast it runs in this particular sequence.
Two papers from Clarke's laboratory at UCLA measured the rates in model peptides. Geiger and Clarke, Journal of Biological Chemistry 1987, found that the hexapeptide Val-Tyr-Pro-Asn-Gly-Ala deamidated through the succinimide with a half-life of only 1.4 days at 37°C and pH 7.4, that replacing the asparagine with aspartate slowed succinimide formation 34-fold, and that replacing the glycine with a bulkier leucine or proline slowed degradation 33- to 50-fold. Stephenson and Clarke, in the same journal in 1989, measured a series of Val-Tyr-Pro-X-Y-Ala peptides and found asparagine 13 to 36 times faster than aspartate at position X, and at position Y glycine 6.5 to 17.6 times faster than alanine, with serine 1.6 to 4.5 times faster than alanine.
| Residue pair | Relative rate | Source |
|---|---|---|
| Asn-Gly | Fastest measured; half-life 1.4 days at 37°C in the 1987 hexapeptide | Geiger and Clarke 1987 |
| Asp-Gly | About 34-fold slower than Asn-Gly | Geiger and Clarke 1987 |
| Asn-Ala versus Asn-Gly | Alanine 6.5 to 17.6 times slower than glycine at the following position | Stephenson and Clarke 1989 |
| Asp versus Asn, same following residue | Aspartate 13 to 36 times slower | Stephenson and Clarke 1989 |
| Asp-Ala (DSIP, positions 5 and 6) | Slowest combination of those measured: aspartate, followed by alanine | Both papers, by combination |
Relative rates of succinimide formation in model hexapeptides at pH 7.4, from the abstracts of Geiger and Clarke (1987) and Stephenson and Clarke (1989). DSIP's own pair is in the last row.
The point for DSIP is that its pair is Asp-Ala, not Asp-Gly. The glycines in the sequence sit before the aspartate, not after it, and what governs the rate is the residue after. So of the combinations Clarke's group measured, DSIP carries the slowest one, and the Gly-Gly stretch ahead of the aspartate adds flexibility rather than a faster route. This is a slower site than the classic hot spot, and it is still the site. In solution at neutral pH and ordinary temperatures the reaction runs on a timescale of weeks to months rather than days, and in the dry solid at -20°C it is effectively arrested, because the rearrangement needs water and backbone mobility.
What the isomer looks like on a certificate
Isoaspartyl DSIP has the same formula and the same mass as the parent, so mass spectrometry does not see it. Reversed-phase HPLC usually does, as a second peak close to the main one, since moving the backbone through the side chain changes the shape and the retention. On an original certificate for a fresh lot that peak should be small or absent. On a re-test of material that has been in solution, or held warm, it is the peak to look for: same mass, slightly different retention, growing with time.
Tryptophan oxidation is the other change to expect and it is mass-visible, adding 16 or 32 Da to the parent, so a re-test that shows a peak at 865 or 881 is reporting oxidation at position 1. Light accelerates it, which is the practical reason behind the catalogue's instruction to protect the lyophilised material from light.
Storage and re-test, as the sequence dictates
The record's storage line is the catalogue's standard one: lyophilised at -20°C, protected from light and moisture, with the reconstituted solution refrigerated and used according to laboratory protocol. The chemistry above says why each clause matters for this sequence in particular. Cold and dry arrest the succinimide route; dark slows tryptophan oxidation; and once water is present the aspartate clock starts, slowly, at the rate the Asp-Ala pair allows.
For re-testing, re-test dates versus expiry dates covers the difference between the two. For DSIP the re-test should be read against the original trace: the isoaspartyl shoulder at the same mass, and any peak 16 or 32 Da above the parent, are the two findings the sequence predicts. A lot that shows neither after storage has behaved as the chemistry says a cold, dry nonapeptide with no cysteine should.
Strengths by mass
At 848.81 g/mol, 5 mg is about 5.9 micromoles and 10 mg about 11.8 micromoles, before correcting for what the vial holds besides peptide. Net peptide content covers that correction. For this sequence the counterion share is likely to be small, since the only basic site that can hold an acidic counterion such as trifluoroacetate is the N-terminal amine, so the non-peptide mass is more plausibly water and residual salt than counterion. The certificate's content figure, not the label, is still the number to use.
What to check before ordering
- The sequence on the certificate against Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, and an observed mass within a dalton of 848.8.
- A single main HPLC peak, with the method stated, and no near-neighbour at the same mass.
- The net peptide content and the water figure, since the label is lyophilised solid.
- Both dates on the certificate, and the storage history if the lot is not fresh.
- That the certificate names the lot on the vial.
DSIP is a short, well-characterised sequence whose documentation is easy to verify and whose name promises more than the literature supports. A buyer who works from the sequence, the mass and the certificate, and treats the name as history, has the measure of it.