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A spin labelling study of glycopeptides and adamantylpeptides entrapped into liposomes

Liposome-drug interactions are investigated with the aim to develop an efficient drug-delivery system that will increase accumulation of the drug at the targeted site in the human body. For an efficient delivery of drugs to targeted cells a better understanding of lipid-drug interactions is necessary. Specially, physical nature of weak interactions between liposomes and compounds of pharmacological interest, like small peptides is missing. The peptides of particular interest for pharmacological applications are those which exhibit immunological and tumoricidal activity. Compounds comprising the elements of bacterial peptidoglycan structure have been recognized as an important group of immunomodulators. Peptidoglycan monomer (GlcNAc-MurNAc-L-Ala-D-isoGlnmesoDAP(wNH2)-D-Ala-D-Ala, PGM) and its derivatives were prepared and their biological activitites were measured [1, 2]. The requirement for lipophilicity led to the idea to synthetize a novel class of small peptides, adamantyltripeptides, represented by D, L-(adamant-2-yl)glycyl-L-alanyl-D-isoglutamine[3] and to study their immunostimulating activity [4]. Adamantyl-moieties have been used primarily to modify the potency of the pharmacological substances already recognized as drugs but 1-amino-adamantane is a known drug by itself ("Symmetrel"). 1-adamantyl-amine derivatives of the peptides: L-Tyr-Gly and L-Tyr-Gly-Gly, were synthetized and their structure and biological activity are studied in "R. Boskovic" Institute [5]. In order to improve the pharmacological activity of these compounds the examined peptides were incorporated into liposomes of chosen composition, and the effect of these peptides on the membrane structure was studied by spin labelling methods. Reference 1. J. Tomašić, I. Hršak "Peptidoglycan Monomer Originating from Brevibacterium divaricatum - its Metabolism and Biological Activities in the Host". u Surface Structures of Microorganisms and Their Interaction with the Mammalian Host (E. Schrinner, M.H. Richmond, G. Seidl i U. Schwartz, Ed.) VCH Gesellschaft, (1987) 113-121. 2. B. Halassy Špoljar, T. Čimbora, I. Hanzl-Dujmović, B. Dojnović, A. Sabioncello, M. Krstanović, J. Tomašić, Influence of Adjuvant-active Peptidoglycan Monomer on specific T cell Responses in Mice, Vaccine, 20 (2002) 3543-3550. 3. B. Vranešić, J. Tomašić, S. Smerdel, D. Kantoci, F. Benedetti, Synthesis and Antiviral of Novel Adamantylpeptides, Helv. Chim. Acta 76 (1993) 1752-1758. 4. J. Tomašić, I. Hanzl-Dujmović, B. Špoljar, B. Vranešić, M. Šantak, A. Jovičić, Comparative Study of the Effects of Peptidoglycan Monomer and Structurally Related Adamantyltripeptides on Humoral Immune Response to Ovalbumin in the Mouse, Vaccine, 18 (2000) 1236-1243. 5. Š. Horvat, L. Varga-Defterdarović, J. Horvat, R. Jukić, D. Kantoci, N.N. Chung, P.W. Schiller, , L. Biesert, A. Pfuetzner, H. Suhartono, H. Ruebsamen-Waigmann, Synthesis and Bioactivity Studies of 1-Adamantanamine Derivatives of Peptides, J. Peptide Science 1 (1995) 303-310.

electron spin resonance spectroscopy; spin labels; peptidoglycan monomer adamantilpeptides; liposomes

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