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Peptidoglycans as promoters of slow-wave sleep. II. Somnogenic and pyrogenic activities of some naturally occurring muramyl peptides; correlations with mass spectrometric structure determination.
Open accessAbstract
The structures of components of the sleep-promoting material purified from human urine were established by fast atom bombardment-mass spectrometry, as reported in the accompanying paper (Martin, S. A., Karnovsky, M. L., Krueger, J. M., Pappenheimer, J. R., and Biemann, K. (1984) J. Biol. Chem. 259, 12652-12658). We report here that two substances isolated from that preparation, viz. N-acetylglucosaminyl-1,6 -anhydro-N-acetylmuramyl-Ala-gamma-Glu-diaminopimelyl-Ala) and that compound lacking the terminal alanine, are active as somnogens. Cerebro-intraventricular administration of 1 pmol of the glycotetrapeptide was sufficient to induce prolonged excess sleep in rabbits. A similar substance obtained from Brevibacterium divaricatum in which the free carboxyls of the glutamic and diaminopimelic moieties, indicated above, were amidated (N-acetylglucosaminyl-1,6-anhydro-N-anhydromura-myl-Ala-iso- Gln- epsilon-amido-diaminopimelyl -Ala-Ala) was not active as a promoter of slow-wave sleep. Deamidation of this peptide to a mixture of the free dicarboxylic forms produced a somnogenic substance. Our findings show that in addition to the muramyl form of peptidoglycan monomers, the anhydro muramyl form, with no reducing end, is compatible with somnogenic activity. Furthermore, the data obtained with a natural product amplify our earlier observations with smaller synthetic molecules of the importance of amidation/deamidation in the structure-activity relationships of muramyl peptides.
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“The first bacterial component demonstrated to alter sleep was a specific muramyl peptide derived from bacterial cell wall peptidoglycans (Krueger et al, 1984).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Krueger et al, 1984
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Metadata
- Authors
- Krueger, J. M., Karnovsky, M. L., Martin, S. A., Pappenheimer, J. R., Walter, J., & Biemann, K.
- Affiliations
- Massachusetts Institute of Technology (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1984-10
- Volume
- 259
- Issue
- 20
- Pages
- 12659-12662
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1588673077
- Cited by
- 111
- References
- 15
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 4
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- peptidoglycan, slow-wave sleep, muramyl peptides, pyrogenicity, structure-activity relationship, deamidation, amidation, human urine
- MeSH terms
- Acetylmuramyl-Alanyl-Isoglutamine, Animals, Biological Assay, Body Temperature, Cerebral Ventricles, Glycopeptides, Humans, Male, Peptidoglycan, Rabbits, Sleep Stages, Mass Spectrometry, Structure-Activity Relationship
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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