Synthesis, structural characterization and biological activity of mannosylated desmuramyl peptides
| Autor: | Paurević, Marija |
|---|---|
| Přispěvatelé: | Ribić, Rosana |
| Jazyk: | chorvatština |
| Rok vydání: | 2021 |
| Předmět: |
2-aminoadamantane-2-carboxylic acid
mannose desmuramil-dipeptid manoza molekulsko-dinamičke simulacije desmuramyl dipeptide molecular dynamics simulations PRIRODNE ZNANOSTI. Kemija NATURAL SCIENCES. Chemistry NOD2 receptor imunomodulacijska aktivnost immunomodulatory activity udc:54(043.3) Kemija. Kristalografija. Mineralogija 2-aminoadamantan-2-karboksilna kiselina Chemistry. Crystallography. Mineralogy |
| Popis: | U disertaciji je opisana sinteza novih desmuramil-peptida s ugrađenim adamantanskim aminokiselinama te manoznih derivata peptida s ciljem istraživanja njihovih imunomodulacijskih svojstava i strukturnih karakteristika. Sinteza peptida i glikopeptida je optimirana. Imunomodulacijska aktivnost desmuramil-peptida s ugrađenom 2-aminoadamantan-2-karboksilnom kiselinom i manoznih derivata ispitana je in vivo u mišjem modelu. Učinci sintetiziranih spojeva određeni su temeljem izmjerene ukupne količine specifičnih anti-OVA IgG antitijela i potklasa IgG antitijela te uspoređeni s aktivnošću literaturno opisanog ManAdDMP adjuvanta. Manozilirani derivati pokazali su pojačanu imunostimulacijsku aktivnost, dok se dimanozilirani derivat pokazao najaktivnijim adjuvantom ove serije spojeva. U disertaciji je opisana i sustavna konformacijska analiza odabranih desmuramil-peptida u vodi i DMSO primjenom računalnih metoda i spektroskopije NMR. Provedene su i molekulsko-dinamičke simulacije kompleksa manoziliranih desmuramil-peptida i intaktnog NOD2 receptora te su identificirane ključne aminokiseline za vezanje ove klase spojeva na receptor. In the thesis the synthesis of new desmuramyl peptides with incorporated adamantane amino acids and their mannose peptide derivatives is described. Compounds are prepared in order to investigate their immunomodulatory properties and structural characteristics. Peptide and glycopeptide synthesis were optimized and obtained products were structurally characterized. The immunomodulatory activity of desmuramyl peptides with incorporated 2-aminoadamantane-2-carboxylic acid and mannose derivatives was examined in vivo using a mouse model. The effects of the compounds were determined based on the total amount of specific anti-OVA IgG antibodies and subclasses of IgG antibodies and compared with the activity of the known ManAdDMP adjuvant. Mannosylated derivatives showed enhanced immunostimulatory activity, while the dimanosylated derivative proved to be the most active adjuvant. In the thesis a systematic conformational analysis of selected desmuramyl peptides in water and DMSO was performed using computational modeling and NMR spectroscopy. Molecular dynamics simulations of mannosylated desmuramyl peptide complexes with intact NOD2 receptor were also performed, and key amino acid residues involved in binding have been identified. |
| Databáze: | OpenAIRE |
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