Priprava ključnih prekursora za sintezu potencijalnog imunoadjuvanta - konjugata quillaja saponina i desmuramil-dipeptida

master's thesis

• Title (english): Preparation of key intermediates for the synthesis of potential immunoadjuvant-conjugate of Quillaja saponin and desmuramyl dipeptide
• Author: Andrej Biškup
• Mentor: Đani Škalamera (mentor)
• Committee member: Đani Škalamera (predsjednik povjerenstva)
• Committee member: Aleksandra Maršavelski (član povjerenstva)
• Committee member: Predrag Novak (član povjerenstva)
• Committee member: Vesna Petrović Peroković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2020-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U sklopu ovog diplomskog rada pripravljena su tri ključna prekursora za sintezu konjugata
Quillaja saponina i desmuramil-dipeptida. Saharidni prekursor pripravljen je iz
D-galakturonske kiseline, triterpenski izolacijom iz komercijalno dostupnog ekstrakta kore
drveta Quillaja saponaria, a peptidni iz odgovarajudih aminokiselina. Rad uključuje izolaciju i
karakterizaciju prirodnih spojeva te sintetske metode peptidne i ugljikohidratne kemije. Sva
tri prekursora zahtijevaju odgovarajudi odabir zaštitnih skupina (ortogonalnost i
neortogonalnost), kako bi se broj koraka njihovog uvođenja i uklanjanja minimizirao. Cilj
ovog diplomskog rada jest pronalazak sintetskog puta do ključnih prekursora u pripravi
konjugata Quillaja saponina i desmuramil-dipeptida. Za navedene dvije jedinice poznato je
da svaka zasebno posjeduje izraženu imunoadjuvantsku aktivnost pa je pretpostavka da bi
njihovo povezivanje dovelo do sinergističkog efekta u povedanju te aktivnosti. Dodatno, osim
priprave ciljanog konjugata, prekursori pripravljeni u ovom radu omoguduju pripravu serije
derivata različitih strukturnih karakteristika, čime se otvara mogudnost ispitivanja korelacije
struktura-imunoadjuvantska aktivnost (eng. structure-activity relationship, SAR).

Abstract (english)

In this diploma thesis, three key intermediates needed for the synthesis of Quillaja saponin and
desmuramyl dipeptide conjugate were prepared. The saccharide precursor is prepared starting from
D-galacturonic acid, the triterpene precursor by isolation from the commercially available Quillaja
saponaria tree bark extract, and the peptide precursor by coupling the corresponding amino acids.
This work includes the isolation and characterization of natural compounds and synthetic methods of
peptide and carbohydrate chemistry. All three precursors need the convenient selection of the
protective groups (orthogonality and non-orthogonality), in order to reduce the number of steps for
their introduction and cleavage. The goal of this work is to find a synthetic pathway toward key
intermediates in the synthesis of Quillaja saponin and desmuramyl dipeptide precursor. It is known
that those two units show high immunoadjuvant activity, thus the working hypothesis is that their
linking will lead to the synergistic effect in the enhancement of that activity. Additionally, besides the
preparation of the target compound, the precursors prepared in this work will enable the
preparation of a series of derivatives of different structural characteristics, which will open the
possibility of the investigation of the correlation between structure and immunoadjuvant activity
(SAR).

• Keywords: cjepiva; derivati prirodnih spojeva; desmuramil-dipeptid; imunoadjuvantska aktivnost; Quillaja saponini
• Keywords (english): desmuramyldipeptide; immunoadjuvant activity; natural compound derivates; Quillaja saponins; vaccines
• Language: croatian
• URN:NBN: urn:nbn:hr:217:437206
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2022-09-28
• Created on: 2020-10-13 09:56:37