Key findings
- The original characterization gives the sequence Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, and of nine synthesized peptides covering the full sequence, five fragments, two exchanged-residue analogues and a related tripeptide, only the full synthetic nonapeptide reproduced the electroencephalogram pattern. [1]
- On the apical side of Caco-2 monolayers the peptide was rapidly cleaved, leaving 8.2 percent after two hours with tryptophan as the major fragment, and a three inhibitor combination raised that to 95.1 percent without any intact peptide appearing on the basolateral side. [2]
- In isolated rat brain mitochondria the peptide raised the rate of phosphorylating respiration, the respiratory control ratio and the rate of ADP phosphorylation while leaving uncoupled respiration unchanged. [3]
- Entrapment in a positively charged macroporous copolymer reached close to complete loading against 2 to 6 percent on a negatively charged matrix, and release occurred in saline buffers but not in water or 25 percent ethanol. [4]
Identity and structure
- Origin
- Isolated from rabbit and then prepared synthetically together with five fragment peptides, two analogues with two residues exchanged and a related tripeptide [1]
- Reported fragments
- Cleavage in intestinal cell culture yielded tryptophan, Trp-Ala and, under partial peptidase inhibition, Trp-Ala-Gly-Gly-Asp-Ala-Ser [2]
- Charge behaviour
- Binds a positively charged macroporous copolymer almost quantitatively and a negatively charged one poorly, which the authors attribute to ionic interaction [4]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
No receptor for this peptide is identified in the cited work. The original characterization instead establishes sequence specificity by elimination, since neither the five metabolic fragments nor the two exchanged-residue analogues nor the related tripeptide reproduced the measured electroencephalogram change. [1]
The cellular work points at bioenergetics rather than at signalling. Polarographic oxygen measurements on isolated rat brain mitochondria and brain homogenates show a selective rise in phosphorylating respiration and in the respiratory control ratio, with the uncoupled rate unchanged, which places the effect on the coupling of respiration to ATP production. [3]
Immunohistochemistry maps peptide-like immunoreactivity to hypothalamic neurosecretory territory. Cell bodies were sparse and scattered through the ventrolateral septum, the diagonal band of Broca, the preoptic areas and the arcuate nucleus, while dense fiber networks appeared in the median eminence and pituitary stalk with many fibers apposed to capillaries. [5]
Research findings
Preclinical in vivo
- System
- Rabbits exposed to each of the nine synthetic peptides in turn under double-blind conditions, 58 animals including controls
- Measured
- Neocortical and archicortical electroencephalogram leads, fast-Fourier transformed and analyzed by computer, for delta and spindle pattern content
- Reported
- Only the full synthetic nonapeptide produced significant and specific enhancement of the delta and spindle patterns. The five fragment peptides, the two exchanged-residue analogues and the related tripeptide did not. [1]
In vitro
- System
- Cultured human intestinal epithelial Caco-2 cell monolayers, applied on the apical or the basolateral side
- Measured
- Percentage of intact peptide remaining after two hours, identity of the cleavage fragments, and the effect of bestatin, amastatin, puromycin, diprotin A, Gly-Pro, EDTA, 1,10-phenanthroline, leupeptin and captopril alone or combined, plus apical to basolateral flux
- Reported
- Apical application left 8.2 percent intact after two hours with tryptophan as the major fragment; basolateral application left 70.6 percent. Bestatin barely raised stability but shifted the fragment distribution toward Trp-Ala. Bestatin with diprotin A gave 83.2 percent and revealed a longer fragment blocked by captopril, and all three together gave 95.1 percent. No intact peptide was detected on the basolateral side under any condition. [2]
Ex vivo
- System
- Isolated rat brain mitochondria and rat brain homogenates, with the peptide and the Deltaran preparation built on it tested in parallel
- Measured
- Oxygen consumption by polarography, maximal respiration rates, the phosphorylating rate V3, the uncoupled rate in the presence of dinitrophenol, the respiratory control ratio and the rate of ADP phosphorylation
- Reported
- The phosphorylating rate V3 rose significantly while the uncoupled rate was unchanged, and the respiratory control ratio and the ADP phosphorylation rate both increased. The Deltaran preparation gave the same result in brain homogenates. [3]
Analytical
- System
- Two macroporous polymer matrices, a positively charged dimethylaminoethyl methacrylate copolymer and a negatively charged acrylic acid copolymer, both crosslinked with methylene-bis-acrylamide
- Measured
- Fraction of peptide entrapped in each matrix, and release into water, 25 percent ethanol, 0.9 percent sodium chloride and phosphate buffered saline
- Reported
- Close to complete entrapment in the positively charged matrix against 2 to 6 percent adsorbed on the negatively charged one. Release from the positively charged matrix occurred in the two saline media and not in water or 25 percent ethanol, which the authors attribute to ionic strength. [4]
Ex vivo
- System
- Rabbit brain and hypophysis sections, including colchicine pretreated animals, probed by immunohistochemistry for peptide-like immunoreactivity rather than for the peptide itself
- Measured
- Distribution and density of immunolabeled cell bodies, varicose fibers and terminal-like structures across brain regions and pituitary lobes
- Reported
- Immunoreactivity was predominantly in basal forebrain, hypothalamus and hypophysis. Labeled cell bodies were relatively few even after colchicine, scattered through the ventrolateral septum, the diagonal band of Broca, the preoptic areas and the arcuate nucleus. Dense fiber networks appeared in the median eminence and pituitary stalk with many fibers apposed to capillaries, and most cells of the pars intermedia were immunoreactive. [5]
Preclinical in vivo
- System
- Sprague Dawley rats with focal stroke induced by intraluminal middle cerebral artery occlusion, compared with vehicle and with sham operated animals, the peptide given before occlusion and for seven days after reperfusion
- Measured
- Motor coordination, balance and bilateral asymmetry on a battery of behavioral tests at 1, 3, 7, 14 and 21 days, then infarction volume from serial cryosections
- Reported
- Infarction volume was smaller in the peptide group but the difference was not significant. Rotarod motor performance recovered significantly in the peptide group, which the authors report as accelerated recovery of motor function. [6]
Handling for in-vitro work
- Peptidase sensitivity in cited work
- Rapidly cleaved by aminopeptidase and dipeptidyl peptidase activity in cell culture; combined bestatin, diprotin A and captopril inhibition was needed to keep the peptide largely intact over two hours [2]
- Ionic strength
- Release from a positively charged polymer matrix happened in saline media and not in water or 25 percent ethanol [4]
- Storage
- Lyophilized at -20 °C, dark and dry; reconstituted aliquots kept cold and used promptly
Open questions
- No receptor or binding protein for this sequence is identified in the cited work, so the electroencephalogram specificity rests on the fragment and analogue comparison alone.
- Intact peptide never crossed the intestinal cell monolayer even when the major cleavage routes were inhibited, and the cited authors leave the reason unresolved between an unidentified further pathway and low intrinsic permeability.
- The immunohistochemistry reports immunoreactivity, which may include related epitopes rather than this nonapeptide specifically.
- The mitochondrial result is from isolated organelles and brain homogenate, and the cited work does not establish that the same coupling change occurs in intact cells.
A clinical literature on this peptide exists and concerns finished formulations; it is out of scope for a research material profile.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
- RV-24-0034-1 ↗DSIP · 99.30% HPLC2026-09-16
References
- Schoenenberger GA, Monnier M Characterization of a delta-electroencephalogram (-sleep)-inducing peptide. Proceedings of the National Academy of Sciences of the United States of America. 1977.
- Augustijns PF, Borchardt RT Transport and metabolism of delta sleep-inducing peptide in cultured human intestinal epithelial cell monolayers. Drug metabolism and disposition: the biological fate of chemicals. 1995.
- Khvatova EM, Samartzev VN, Zagoskin PP, et al. Delta sleep inducing peptide (DSIP): effect on respiration activity in rat brain mitochondria and stress protective potency under experimental hypoxia. Peptides. 2003.
- Sukhanova TV, Artyukhov AA, Gurevich YM, et al. Delta-sleep inducing peptide entrapment in the charged macroporous matrices. Materials science & engineering. C, Materials for biological applications. 2014.
- Charnay Y, Bouras C, Vallet PG, et al. Immunohistochemical distribution of delta sleep inducing peptide in the rabbit brain and hypophysis. Neuroendocrinology. 1989.
- Tukhovskaya EA, Ismailova AM, Shaykhutdinova ER, et al. Delta Sleep-Inducing Peptide Recovers Motor Function in SD Rats after Focal Stroke. Molecules (Basel, Switzerland). 2021.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.