Synthesis and Biological Evaluation of New Mannose Derived Immunomodulating Adamantyltripeptides

Abstract

Abstract. A novel class of mannosylated adamantyltripeptides, general formula of which is α-Man-OCH 2 CH(CH 3 )CO-AdGly-L-Ala-D-isoGln, were prepared, characterized, and their possible immunomodulatory properties investigated in some preliminary tests in vivo. All newly synthesized glycopeptides comprise in their structure the adamantylglycyl moiety linked to the dipeptide L-Ala-D-isoGln, as well as mannose. Adjuvant activity of mannosylated adamant-2-yl tripeptides was tested in the mouse model using ovalbumin as an antigen and in comparison to the peptidoglycan monomer (PGM, β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH 2 )-D-Ala-D-Ala).

Mannosylated Liposomes with Built-in Peptidoglycan Based Immunomodulators for Subunit Vaccine Formulations

“…[21][22][23][24][25][26][27] Our previous studies have been focused on the synthesis of novel immunomodulators and potent adjuvant formulations with improved activity. [28][29][30] In recently published paper we described the synthesis of mono-, di-and tetramannosyllipoconjugate, used for mannosylation of liposomes, and studies of interaction of prepared mannosylated liposomes with model lectine, concanavaline A (Con A) by quartz crystal microbalance (QCM). [31] Here we report preparation of mannosylated liposomes with built-in peptidoglycan based immunomodulators, peptidoglycan monomer surface.…”

Advances in Desmuramyl Peptide Research

“…Our group has prepared mannosylated adamantyl tripeptides with immunostimulating activity. [42] Mannose was attached to the desmuramyl dipeptide because it may contribute to the recognition of the adjuvant compound by specific mannose receptors expressed at immune cells. It is known that mannosylated drug delivery systems enhance uptake and activation of dendritic cells and increase T cell proliferation.…”

“…[43][44][45][46] Mannosylation of the adamantylated desmuramyl peptides amplified the adjuvant activity in experiments in vivo. [42,46] Different isomers of mannosylated adamantyl tripeptides, regarding the chiral centers introduced at adamantyl glycine and spacer connecting the sugar part to the adamantyl tripeptide were synthesized and biologically evaluated. [42,46] Introduction of mannose has significantly stimulated the immune response.…”

“…[42,46] Different isomers of mannosylated adamantyl tripeptides, regarding the chiral centers introduced at adamantyl glycine and spacer connecting the sugar part to the adamantyl tripeptide were synthesized and biologically evaluated. [42,46] Introduction of mannose has significantly stimulated the immune response. We assume that mannose effects the immune response by mannose receptors family, group I CLRs, present on immunocompetent cells (such as macrophages and dendritic cells).…”

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

“…Up to now, our research was directed towards isomeric desmuramyl peptides containing lipophilic unnatural amino acid, adamantylglycine (AdGly), bound to the N-terminus of L-Ala-D-isoGln dipeptide part as well as their mannosylated derivatives. Different isomers of mannosylated adamantyl tripeptides, regarding the chiral centers introduced at adamantlyglycine and spacer which connect the sugar part to the PGM MDP adamantyltripeptide were synthesized and biologically evaluated [19][20][21]. The best adjuvant activity in experiments in vivo showed the ManAdTP derivative ( Figure 2) which has a D-configuration at the (adamant-1yl)glycine moiety and (R)-configuration on hydroxyisobutyryl linker.…”