Priprava C-glikozilne α-aminokiseline modifikacijom prirodnih monosaharida

master's thesis

• Title (english): Synthesis of C-glycosyl α-amino acid by natural monosaccharides modification
• Author: Maja Ratajec
• Mentor: Irena Škorić (mentor)
• Mentor: Ivanka Jerić (komentor)
• Committee member: Irena Škorić (predsjednik povjerenstva)
• Committee member: Dragana Vuk (član povjerenstva)
• Committee member: Ivanka Jerić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2022-07-07, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Peptidi i proteini su prirodni spojevi koji imaju ključnu ulogu u nizu imunoloških i neuroloških procesa. Djeluju kao neurotransmiteri, hormoni, antigeni i antibiotici, a poremećaji u njihovoj funkciji mogu dovesti do razvoja kroničnih ili infektivnih oboljenja. Unatoč tome, njihova upotreba kao terapeutika ograničena je lošom stabilnošću i bioraspoloživošću. Napredak u strukturnoj optimizaciji, formulaciji i proizvodnji zaslužan je za sve veći broj peptida koji ulaze u klinička ispitivanja i terapijsku primjenu. Nadalje, potreba za kontrolom funkcije peptida dovela je do razvoja peptidomimetika, spojeva koji oponašaju sekundarne strukture proteina, a time i njihove funkcije. U pripravi takvih spojeva važnu ulogu imaju neprirodne aminokiseline. Cilj istraživanja u okviru ovog diplomskog rada je sinteza tripeptida s ugrađenom neprirodnom C-glikozilnom α-aminokiselinom. Za dobivanje C-glikozilne jedinice korištena je dijastereoselektivna Passerinijeva reakcija. Kao izvor C-glikozilne jedinice korišteni su izopropilidenima zaštićeni aldehidi dobiveni iz odgovarajućih ugljikohidrata (sorboze i fruktoze). U Passerinijevoj reakciji korišteni su aminokiselinski, odnosno konvertibilni izocijanid koji se vrlo lako ukloni hidrolizom u baznim uvjetima s ciljem dobivanja derivata α-hidroksi C-glikozilnih kiselina. Post-kondenzacijskim modifikacijama α-hidroksi-derivat je preveden u aminokiselinu, koja je ugrađena u dipeptidni i tripeptidni slijed.

Abstract (english)

Peptides and proteins are natural compounds that play a key role in a number of immune and neurological processes. They act as neurotransmitters, hormones, antigens and antibiotics, and disorders in their function can lead to the development of chronic or infectious diseases. Nevertheless, their use as therapeutics is limited by poor stability and bioavailability. Advances in structural optimization, formulation, and manufacturing are responsible for the growing number of peptides entering clinical trials and therapeutic applications. Furthermore, the need to control peptide function has led to the development of peptidomimetics, compounds that mimic the secondary structures of proteins and thus their functions. Unnatural amino acids play an important role in the synthesis of peptidomimetics. The objective of the research proposed in this master thesis is the synthesis of tripeptides with incorporated unnatural C-glycosyl α-amino acid. Diastereoselective Passerini reactions were used to obtain the C-glycosyl unit. Isopropylidene-protected aldehydes derived from the carbohydrates (sorbose and fructose) were used as the source of the C-glycosyl unit. In the Passerini reaction, amino acid or convertible isocyanide was used, which is very easily removed by the hydrolysis under basic conditions in order to obtain α-hydroxy C-glycosyl acid derivatives. By post-condensation modifications the α-hydroxy derivative was converted to an amino acid, which was incorporated into the dipeptide and tripeptide sequences.

• Keywords: C-glikozilne aminokiseline; multikomponentne reakcije; peptidi; peptidomimetici; ugljikohidrati
• Keywords (english): C-glycosyl amino acids; multicomponent reactions; peptides; peptidomimetics; carbohydrates
• Language: croatian
• URN:NBN: urn:nbn:hr:149:260724
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-02-26 15:48:25