DSIP: The Sleep Peptide Nobody Has Found a Gene For

For laboratory research use only. Not for human or veterinary use.

DSIP stands for delta sleep-inducing peptide, and the name has done most of its marketing for nearly fifty years. It was named after one effect seen in rabbits in 1977. Since then, nobody has found the gene that makes it, the protein it would be cut from, or a receptor it acts on, and the controlled human studies were underwhelming. This guide sets out what DSIP is, where the name came from, what the research does and does not show, and what to check on a certificate.

Identity#

The masses are our own calculation from the sequence. Every residue is one of the twenty standard amino acids, and five of the nine are glycine or alanine, which makes DSIP small, flexible and quickly broken down.

Where the name came from#

DSIP was isolated by Schoenenberger, Monnier and colleagues in Basel. Their group electrically stimulated a region of the thalamus in rabbits to bring on sleep, collected material from the blood leaving the brain, and searched it for something that would reproduce the effect. In 1977 they described a nine-residue peptide that, infused into the brain’s fluid-filled ventricles of other rabbits, increased the slow “delta” waves and spindles of deep sleep on the EEG. They named it after that effect.

In the 1978 paper that confirmed the sequence, they synthesised it alongside fragments and altered versions, and tested all of them blind in 61 rabbits. Only the synthetic nonapeptide reproduced the effect, increasing delta activity by about 35% over controls. One detail from that paper matters for anyone reading a certificate today: only the normal α-aspartyl form was highly active, not its β-aspartyl isomer. More on that below.

The missing gene#

Almost every peptide hormone or neuropeptide is cut from a larger precursor protein, encoded by a known gene, and acts through an identified receptor. DSIP has none of the three. A 2006 review, titled “a still unresolved riddle”, put it plainly: the link between DSIP and sleep was never characterised further, partly because no gene, precursor or receptor was found, and the idea of DSIP as a natural sleep factor remains weak. The same authors noted that in their own early work, some synthetic analogues of DSIP promoted deep sleep in rabbits and rats, but DSIP itself did not.

The search has not stopped. In 2011 a Moscow group pointed out that a family of human enzymes, histone demethylases of the JMJD1B type, contains the sequence WKGGNASGE, which differs from DSIP at only two positions. They proposed these proteins as possible precursors of DSIP-like peptides. It is a hypothesis, not a finding.

How it behaves#

• It reaches the brain. In anaesthetised dogs in 1982, DSIP given into the bloodstream appeared intact in the cerebrospinal fluid, at ratios higher than insulin. It was also found bound reversibly to a large carrier molecule in plasma.
• It does not last. In human and rat blood, DSIP was broken down quickly, releasing free tryptophan, in a way that depended on temperature, time and species. Some modified analogues persisted longer, which the authors suggested might explain why analogues sometimes gave stronger effects than DSIP itself.

What has been tested in people#

Through the 1980s, DSIP was given intravenously to people in a series of studies, most of them small and several from the group that discovered it. The early, open studies were encouraging: in 1981, six middle-aged adults with long-standing sleep complaints slept longer and with fewer interruptions after a single dose, with no daytime sedation.

The controlled studies were less so.

• 1987. A double-blind crossover study over four nights found some sleep measures improved against placebo, but the same differences were already present on the baseline nights. The authors concluded the improvement was of little clinical significance.
• 1992, Amsterdam. A double-blind study in 16 adults with long-standing sleep complaints, over three nights, found slightly higher sleep efficiency and shorter time to fall asleep with DSIP. The authors judged the effects weak, partly explained by a chance change in the placebo group, and found no change in how well people felt they had slept.

Two hormone studies in healthy volunteers also found nothing. DSIP did not change growth hormone or prolactin in eight women (1993), and did not change ACTH or cortisol in men, either after a hormone challenge or around a meal (1995). That second result contradicted earlier laboratory work suggesting DSIP held back the stress-hormone axis.

DSIP is not a licensed medicine anywhere. Most of the research on it since the 1990s has been in animals, much of it from Russian laboratories.

What to check on the certificate#

• Mass: 848.81 (monoisotopic 848.33). On a mass spectrum expect the singly charged ion near 849.3 or the doubly charged ion near 425.2.
• The β-aspartyl problem. The inactive β-aspartyl isomer has exactly the same mass as DSIP, so mass spectrometry alone cannot tell them apart. Aspartic acid can rearrange this way during synthesis and storage. Only chromatography separates them, which is why the purity figure, and the method behind it, matters more for DSIP than for many peptides.
• Tryptophan oxidation. The tryptophan at the front is the residue most prone to oxidation. Peaks 16 or 32 mass units heavier than DSIP (about 864.3 or 880.3) point to oxidised material.
• Missing tryptophan. A peak near 662.6 is DSIP without its first residue, a fragment also found in dogs’ cerebrospinal fluid after DSIP was given in 1982.
• Net peptide content and counter-ion. A short peptide carries a meaningful share of counter-ion, usually acetate, and water. Net peptide content is how much of the vial is peptide, and it is not the same number as purity.

Ask about the documentation for the batch we would ship before you order. See also how to read a COA, how to verify one and what a purity figure means.

Handling and storage#

Standard peptide handling applies, with one extra reason to be careful about light: tryptophan oxidises. Store the sealed lyophilised vial cold, dry and in the dark, and let it reach room temperature before opening. Reconstitute by running bacteriostatic or sterile water down the vial wall rather than onto the powder, and swirl rather than shake. Once in solution, keep it refrigerated and use it within its working window. The reconstitution guide, solvent guide and storage guide cover the detail.

What Pioneer supplies#

DSIP is stocked in a 5mg vial, with 2mg and 10mg made to order in one to two weeks.

Quality comes first#

DSIP is a short, unmodified peptide with two weak points: a tryptophan that oxidises and an aspartic acid that can rearrange into an inactive form of the same mass. A mass alone will catch the first and miss the second. Ask about the documentation for the batch we would ship before you order.

Sources#

Each entry links to its PubMed record, where the title and abstract can be read. The descriptions are ours: they say what each paper examined, not what it is claimed to show. Records checked on PubMed on 29 October 2026.

1. Schoenenberger GA, Monnier M (1977). Proc Natl Acad Sci U S A 74(3):1282–6. The first description of DSIP: isolated from rabbits, its sequence, and blind EEG testing of the synthetic peptide and related fragments in rabbits. PubMed 265572
2. Schoenenberger GA, Maier PF, Tobler HJ, et al. (1978). Pflugers Arch 376(2):119–29. Sequence confirmation and synthesis, with blind EEG testing of nine synthetic peptides in 61 rabbits, comparing the α-aspartyl and β-aspartyl forms. PubMed 568769
3. Banks WA, Kastin AJ, Coy DH (1982). Pharmacol Biochem Behav 17(5):1009–14. Whether DSIP and two analogues given into the bloodstream of anaesthetised dogs reach the cerebrospinal fluid, and its binding to a carrier molecule in plasma. PubMed 6897451
4. Graf MV, Saegesser B, Schoenenberger GA (1987). Peptides 8(4):599–603. How quickly DSIP and two analogues break down in human and rat blood. PubMed 3628078
5. Schneider-Helmert D, Schoenenberger GA (1981). Experientia 37(9):913–7. Open study of a single intravenous dose in six middle-aged adults with long-standing sleep complaints, recording sleep in the laboratory. PubMed 7028502
6. Monti JM, Debellis J, Alterwain P, et al. (1987). Int J Clin Pharmacol Res 7(2):105–10. Double-blind placebo-controlled crossover study over four nights, recording sleep in the laboratory. The authors judged the changes of little clinical significance. PubMed 3583493
7. Bes F, Hofman W, Schuur J, et al. (1992). Neuropsychobiology 26(4):193–7. Double-blind placebo-controlled study in 16 adults with long-standing sleep complaints over three nights. The authors judged the effects weak. PubMed 1299794
8. Giusti M, Carraro A, Porcella E, et al. (1993). Psychoneuroendocrinology 18(1):79–84. Growth hormone and prolactin measured in eight healthy women after DSIP, with and without an arginine challenge, against placebo. PubMed 8475226
9. Späth-Schwalbe E, Schäfer A, Uthgenannt D, et al. (1995). Psychoneuroendocrinology 20(3):231–7. ACTH and cortisol measured in healthy men after DSIP or placebo, following a hormone challenge and around a meal. PubMed 7777652
10. Kovalzon VM, Strekalova TV (2006). J Neurochem 97(2):303–9. Review of what is and is not known about DSIP, including the absence of an identified gene, precursor protein or receptor. PubMed 16539679
11. Mikhaleva II, Prudchenko IA, Ivanov VT, et al. (2011). Peptides 32(4):826–31. Database search proposing a family of human enzymes that contain a DSIP-like sequence as possible precursors. PubMed 21262293

In our catalogue#

• DSIP — 5mg in stock; 2mg and 10mg made to order

Pioneer Research Peptides — UK supplier of research peptides for laboratory use. Ask about batch documentation before you order.

For laboratory research use only — not for human consumption. 18+.