DSIP

DSIP is a nine-residue peptide. Its initials are the name given at isolation, delta sleep inducing peptide, which records an experimental context rather than a function. Four of the nine residues are glycine or alanine, leaving the backbone unusually flexible, and two acidic residues sit at the tail.

The peptide was isolated from the cerebral venous blood dialysate of rabbits by the Schoenenberger and Monnier group in Basel and characterised and synthesised in 1977. The name records the experimental context of that isolation rather than an established function, and the distinction matters here more than usual.

Structurally it is entirely unmodified: Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, all L-residues, with a free N-terminal amine and a free C-terminal acid, no amidation and no disulfide. Four glycine or alanine residues give the backbone unusual conformational freedom, and solution studies by NMR, circular dichroism, infrared spectroscopy and fluorescence describe a dynamic equilibrium between unordered and folded states rather than a single structure. The N-terminal tryptophan is the only aromatic residue, which makes it both the molecule's sole absorbance chromophore and its most oxidation-prone side chain.

Two things about this peptide are more uncertain than its forty-year presence in the literature suggests, and both are worth knowing. No precursor gene or precursor protein has ever been identified for it; its entry in the protein sequence databases exists at protein level only, with no nucleotide cross-reference. And no specific receptor or binding protein has been isolated, with a peer-reviewed review describing the evidence for its identity as a sleep peptide as poorly documented and weak. A related caution on naming: the gene DSIPI, also called TSC22D3 or GILZ, was named for immunoreactivity with this peptide and is an unrelated protein; it should not be cited as this peptide's gene.

The reported molecular observations are indirect. In rat median eminence preparations the peptide inhibited somatostatin release in a manner blocked by the dopamine antagonist pimozide, which the authors read as dopaminergically mediated rather than as a direct receptor action; calcium-dependent release of met-enkephalin from rat synaptosomes has also been reported, as have changes in antioxidant enzyme activities in rodent tissue preparations.

One property has been measured cleanly, and it is a transport property rather than a pharmacological one. In vascularly perfused guinea-pig brain the peptide crosses the blood-brain barrier by a high-affinity saturable mechanism that is self-inhibited by unlabelled peptide and, interestingly, by L-tryptophan. Against that, it is rapidly degraded in human and rat blood in a species-, time- and temperature-dependent manner; the phosphorylated serine-7 variant degrades more slowly. No numeric plasma half-life has been published.