engleski

The Effect of Chemical Structure and Stereochemistry on Interactions of Immunomodulatory Peptides with Lipid Bilayers in Liposomes

Adjuvants are compounds that are used to enhance the immune response of the host to an antigen. Among the others the peptidoglycan fragments were recognized as potent immunomodulators especially low molecular weight fragments that are mostly devoid of the toxic properties characteristic for large peptidoglycans, but still retain marked immunomodulating activity. Our studies concern the peptidoglycan monomer, GlcNAc-MurNAc-L-Ala-D-isoGlnmesoDAP-D-Ala-D-Ala (PGM), the natural compound originating from the Brevibacterium divaricatum peptidoglycan, its semisynthetic derivatives (Boc-Tyr-PGM and (Adamant-1-yl)-acetyl-PGM) and synthetic adamantyltripeptides D- and L-(adamant-2-yl)-Gly-L-Ala-D-isoGln. All the examined compounds are water-soluble, non-toxic and non-pyrogenic substances and their chemical structure has been completely defined. Biological activity of the prepared compounds has been continuously investigated and numerous papers were reported. In order to slow down their hydrolytic inactivation and thus achieve a prolonged biological action they are incorporated into liposomes. The interactions of incorporated compounds with phospholipids in liposomal bilayers were investigated by electron paramagnetic resonance spectroscopy. The spin labelled fatty acids, n-doxyl-stearic acids (n=5, 7, 16)were used to investigate the interaction of tested compounds with negatively charged multilamellar liposomes. The entrapment of the Boc-Tyr-PGM and adamantyltripeptides affected the motional properties of all spin labelled lipids, while the entrapment of PGM and (Adamant-1-yl)-acetyl-PGM had no effect.

peptidoglycan monomer; adamantyltripeptides; liposomes; ESR

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