DSIP 5 mg

DSIP is a linear nonapeptide - nine amino acids joined end to end - with the sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, written WAGGDASGE in one-letter code. The molecular formula is C35H48N10O15 and the molecular weight is 848.8 g/mol. The chain carries no basic residues; the only ionisable side chains are the carboxylate of aspartate at position 5 and the carboxylate of glutamate at position 9, so the molecule sits at a net negative charge at physiological pH. Both termini are free - an unprotected N-terminal tryptophan and an unprotected C-terminal glutamic acid - with no amidation, acetylation or disulfide bridging; this is the structure recorded for PubChem CID 68816 and for UniProt P01158, the rabbit DSIP entry. The single tryptophan is the only aromatic residue in the sequence and therefore the only strong UV chromophore, which is what makes 280 nm quantitation practical.

The name is historical rather than functional. Schoenenberger's 1984 review in European Neurology records that from 1963 to 1970 his group established humoral transmission of delta-wave (slow-wave sleep) EEG activity in rabbits by intracerebroventricular infusion of extracorporeal dialysate taken from the blood of donor animals kept asleep by electrical stimulation of the ventromedian intralaminar thalamus, and that from 1970 to 1977 the group isolated, characterised and synthesised the nonapeptide held responsible for that effect. Monnier and colleagues published the side-by-side comparison of the original isolate and the synthetic nonapeptide in Experientia in 1977. Kovalzon and Strekalova, writing in the Journal of Neurochemistry in 2006, date the isolation to 1977 and state that no DSIP gene, protein or related receptor has been isolated in the decades since, and that the DSIP structure is different from any other known representative of the various peptide families.

On stability, Schoenenberger reported in that same 1984 paper that the half-life for proteolytic split-off of tryptophan by brain slices and homogenates is 15 minutes, and that endogenous immunoreactive DSIP-like material in plasma, urine and cerebrospinal fluid was found bound to a larger protein and thereby protected from proteolysis. That 15-minute figure is an in vitro brain-tissue measurement, not a blood or plasma half-life; no plasma half-life appears on this page because none could be confirmed against primary literature. Material is supplied as a lyophilised powder specified at 99% or higher purity by HPLC.

The published record on DSIP is unusual: it is large by volume, spread across four decades and several languages, and openly contested on its central question. Graf and Kastin surveyed it in Neuroscience and Biobehavioral Reviews in 1984, describing DSIP as a nonapeptide of molecular weight 849 and reporting that it was shown to induce mainly delta sleep in rabbits, rats, mice and humans, whereas in cats the effect on REM sleep was more pronounced. The same authors published an updated survey, titled an update, in Peptides in 1986. Kovalzon and Strekalova revisited the field in 2006 under the title a still unresolved riddle and concluded that the hypothesis regarding DSIP as a sleep factor is, in their words, extremely poorly documented and still weak - a direct challenge to the peptide's own name.

The most quantitatively explicit rodent work is Iyer, Marks, Kastin and McCann in the Proceedings of the National Academy of Sciences in 1988. Male rats were deprived of sleep for four hours by placing them on a slowly rotating wheel. After removal from the wheel the authors recorded a significant increase in plasma growth hormone concentrations (P less than 0.01) and in the amount of slow-wave sleep (P less than 0.001) above initial values. Both increases were blocked by microinjection of a highly specific antiserum to DSIP into the third cerebral ventricle, while control rats given an equal volume of normal rabbit serum showed the increases intact. The authors wrote that the results suggest DSIP can be a physiological stimulus for sleep-related growth hormone release as well as for the induction of slow-wave sleep.

Human data exist but are old and small. Schneider-Helmert summarised several investigations in European Neurology in 1984, reporting that two studies showed improvement of sleep following single pre-sleep injections in insomnia patients, that repeated administrations indicated a build-up with normalisation of sleep structure after four administrations, and that repeated morning injections and twice-daily dosing produced different response patterns. These are summaries of small single-group reports from the 1980s rather than modern controlled trials, and no contemporary randomised replication has been published. No dose figures from that clinical work are reproduced here.

Two lines of work look at DSIP outside sleep. Khvatova and colleagues reported in Peptides in 2003 on respiration activity in isolated rat brain mitochondria and on stress-protective potency under experimental hypoxia. Separately, Popovich and colleagues ran a lifetime study in female SHR mice published in Mechanisms of Ageing and Development in 2003: 54 animals per group were injected subcutaneously for five consecutive days every month from three months of age with either saline or 2.5 micrograms per mouse (approximately 100 micrograms per kilogram) of a DSIP-containing preparation. Relative to controls the authors reported a 22.6% decrease in the frequency of chromosome aberrations in bone marrow cells, no influence on mean life span, a 17.1% increase in the life span of the last 10% of survivors, a 24.1% increase in maximum life span, and a 2.6-fold decrease in total spontaneous tumour incidence.

Taken together, the literature is best read as an unresolved case rather than a settled one. There is a documented isolation history, a structure confirmed across independent chemical registries, a body of animal EEG and neuroendocrine work, and a handful of small human reports - alongside an explicit 2006 argument from within the field that the sleep hypothesis remains poorly documented and that the gene, protein and receptor are all still missing. Anyone designing work with this compound should read Kovalzon and Strekalova before the older reviews.