Abstract
Sleep-promoting activities of muramyl dipeptide (MDP) (NAc-Mur-L-ala-D- isogln) and the naturally occurring muramyl peptide(s), factor S, have recently been demonstrated. We now have amplified our understanding of structural requirements for somnogenic activity. The effects of several analogs of MDP on rabbit slow-wave sleep are presented and these results are compared to the dose-response relationship for MDP. Some tentative conclusions as to structural requirements for somnogenic activity are presented; most notably, amidation of the free gamma- carboxyl of MDP and several of its analogs resulted in the loss of somnogenic activity. MDP also can induce febrile and immunostimulatory responses. In the present paper, we show that some analogs possess immunostimulatory and pyrogenic activity but not somnogenic activity, thus suggesting that these biological activities of muramyl peptides may, in part, be mediated by separate mechanisms.
Full Text
The Full Text of this article is available as a PDF (598.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Chedid L., Parant M., Parant F., Lefrancher P., Choay J., Lederer E. Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs. Proc Natl Acad Sci U S A. 1977 May;74(5):2089–2093. doi: 10.1073/pnas.74.5.2089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ellouz F., Adam A., Ciorbaru R., Lederer E. Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1974 Aug 19;59(4):1317–1325. doi: 10.1016/0006-291x(74)90458-6. [DOI] [PubMed] [Google Scholar]
- Fencl V., Koski G., Pappenheimer J. R. Factors in cerebrospinal fluid from goats that affect sleep and activity in rats. J Physiol. 1971 Aug;216(3):565–589. doi: 10.1113/jphysiol.1971.sp009541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-Arrarás J. E. Effects of sleep-promoting factor from human urine on sleep cycle of cats. Am J Physiol. 1981 Oct;241(4):E269–E274. doi: 10.1152/ajpendo.1981.241.4.E269. [DOI] [PubMed] [Google Scholar]
- Kaku M., Yagawa K., Nagao S., Tanaka A. Enhanced superoxide anion release from phagocytes by muramyl dipeptide or lipopolysaccharide. Infect Immun. 1983 Feb;39(2):559–564. doi: 10.1128/iai.39.2.559-564.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kotani S., Watanabe Y., Shimono T., Harada K., Shiba T. Correlation between the immunoadjuvant activities and pyrogenicities of synthetic N-acetylmuramyl-peptides or -amino acids. Biken J. 1976 Mar;19(1):9–13. [PubMed] [Google Scholar]
- Krueger J. M., Bacsik J., García-Arrarás J. Sleep-promoting material from human urine and its relation to factor S from brain. Am J Physiol. 1980 Feb;238(2):E116–E123. doi: 10.1152/ajpendo.1980.238.2.E116. [DOI] [PubMed] [Google Scholar]
- Krueger J. M., Pappenheimer J. R., Karnovsky M. L. Sleep-promoting effects of muramyl peptides. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6102–6106. doi: 10.1073/pnas.79.19.6102. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krueger J. M., Pappenheimer J. R., Karnovsky M. L. The composition of sleep-promoting factor isolated from human urine. J Biol Chem. 1982 Feb 25;257(4):1664–1669. [PubMed] [Google Scholar]
- Lederer E. Synthetic immunostimulants derived from the bacterial cell wall. J Med Chem. 1980 Aug;23(8):819–825. doi: 10.1021/jm00182a001. [DOI] [PubMed] [Google Scholar]
- Lefrancier P., Choay J., Derrien M., Lederman I. Synthesis of N-acetyl-muramyl-L-alanyl-D-isoglutamine, an adjuvant of the immune response, and of some n-acetyl-muramyl-peptide analogs. Int J Pept Protein Res. 1977;9(4):249–257. doi: 10.1111/j.1399-3011.1977.tb03488.x. [DOI] [PubMed] [Google Scholar]
- Lefrancier P., Derrien M., Jamet X., Choay J., Lederer E., Audibert F., Parant M., Parant F., Chedid L. Apyrogenic, adjuvant-active N-acetylmuramyl-dipeptides. J Med Chem. 1982 Jan;25(1):87–90. doi: 10.1021/jm00343a018. [DOI] [PubMed] [Google Scholar]
- Lefrancier P., Derrien M., Lederman I., Nief F., Choay J., Lederer E. Synthesis of some new analogs of the immunoadjuvant glycopeptide MDP (N-acetyl-muramyl-L-alanyl-D-isoglutamine). Int J Pept Protein Res. 1978 Apr;11(4):289–296. doi: 10.1111/j.1399-3011.1978.tb02851.x. [DOI] [PubMed] [Google Scholar]
- Pabst M. J., Johnston R. B., Jr Increased production of superoxide anion by macrophages exposed in vitro to muramyl dipeptide or lipopolysaccharide. J Exp Med. 1980 Jan 1;151(1):101–114. doi: 10.1084/jem.151.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pappenheimer J. R., Koski G., Fencl V., Karnovsky M. L., Krueger J. Extraction of sleep-promoting factor S from cerebrospinal fluid and from brains of sleep-deprived animals. J Neurophysiol. 1975 Nov;38(6):1299–1311. doi: 10.1152/jn.1975.38.6.1299. [DOI] [PubMed] [Google Scholar]
- Riveau G., Masek K., Parant M., Chedid L. Central pyrogenic activity of muramyl dipeptide. J Exp Med. 1980 Oct 1;152(4):869–877. doi: 10.1084/jem.152.4.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yapo A., Petit J. F., Lederer E., Parant M., Parant F., Chedid L. Fate of two 14C labelled muramyl peptides: Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm and Ac-Mur-L-Ala-gamma-D-Glu-meso-A2pm-D-Ala-D-Ala in mice. Evaluation of their ability to increase non specific resistance to Klebsiella infection. Int J Immunopharmacol. 1982;4(3):143–149. doi: 10.1016/0192-0561(82)90042-x. [DOI] [PubMed] [Google Scholar]