The delta EEG (sleep)-inducing peptide (DSIP). XI. Amino-acid analysis, sequence, synthesis and activity of the nonapeptide

This is paper XI in the Schoenenberger-Monnier DSIP series and the foundational primary characterization of the peptide that defined the modern endogenous-sleep-factor literature. The Basel group had previously isolated a sleep-promoting fraction from cerebral venous blood of rabbits in which slow-wave EEG had been induced by electrical stimulation of the intralaminar thalamic area; this 1978 paper reports the amino-acid analysis, full sequence determination (Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu), chemical synthesis of the nonapeptide, and direct comparison of natural and synthetic DSIP in recipient rabbits. The synthetic peptide reproduced the natural fraction's effects: enhanced delta and spindle EEG activity characteristic of orthodox slow-wave sleep, with the mean increase in delta-band power reaching approximately 35% in neocortex and limbic cortex compared to control animals. The paper established DSIP as the first sequenced and synthesized candidate endogenous sleep factor and opened the field of sleep neuropeptide research that has continued through the discovery of orexin, prostaglandin D2, and other sleep-regulatory molecules.

This is a 1978 rabbit-EEG characterization paper, not a human clinical trial. The translation from rabbit slow-wave EEG to human sleep architecture is well-established as an experimental paradigm but does not by itself predict clinical efficacy in human insomnia. The receptor mechanism by which DSIP produces its effects was not identified in this paper and, remarkably, has not been definitively identified in the nearly five decades of subsequent research — DSIP remains one of the most-studied peptides without a confirmed primary receptor. Subsequent human clinical work in chronic insomnia produced mixed results; the effect sizes seen in disturbed-sleep populations are modest and the molecule never advanced to a major clinical-development program for sleep indications. Read the paper as the foundational discovery and characterization document for the molecule, not as evidence of clinical utility in modern insomnia treatment, and keep the receptor-mechanism gap in mind when interpreting downstream claims about DSIP's actions.