Molekulsko samoudruživanje i samoreplikacija kratkih amfifilnih peptida

master's thesis

• Title (english): Molecular self-assembly and self-replication of short amphiphilic peptides
• Author: Ramona Petko
• Mentor: Silvana Raić-Malić (mentor)
• Mentor: Leo Frkanec (komentor)
• Committee member: Silvana Raić-Malić (predsjednik povjerenstva)
• Committee member: Irena Škorić (član povjerenstva)
• Committee member: Leo Frkanec (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2024-09-10, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Cilj ovog rada bio je sintetizirati i okarakterizirati spoj (S)-11-(2-heptanamido-3-(1H-imidazol-4-il)propanamido)-N-(piridin-4-ilmetil)undekanamid hidroklorid (7a), derivat
L-histidina (L-His), kao potencijalni gelator male molekulske mase (LMWG, eng. low molecular weight gelator) amfifilnih svojstava. Ispitan je potencijal molekulskog samoudruživanja ciljanog spoja, odnosno formiranja hidrogelova, kao i sposobnost koordinacije Zn2+. Nadalje, istražena je katalitička aktivnost novosintetiziranog spoja pri hidrolitičkoj reakciji raspada p-nitrofenil acetata (p-NPA) na p-nitrofenol (p-NP), koja modelira proces hidrolize prirodnih estera u biološkim sustavima. Prethodno sintetizirani spojevi, strukturni analozi spoja 7a s različitom aminokiselinom (7b – derivat L-fenilalanina, 7c – derivat L-fenilglicina i 7d – derivat L-triptofana) također su ispitani na mogućnost stvaranja kompleksa sa Zn2+ i katalitičko djelovanje. Mjerenja su provedena metodama UV/Vis spektroskopije. Novosintetizirani spoj 7a u svojoj strukturi sadrži dug alifatski lanac, aminokiselinu L-His i terminalni 4-pikolilamin. Njegova priprava uspješno je provedena u 7 stupnjeva: 1. zaštićivanje 11-aminoundekanske kiseline (AUDA) Boc-skupinom (1);
2. aktivacija spoja 1 pomoću N-hidroksisukcinimida (NHS) (3); 3. supstitucija sukcinimidne skupine spoja 3 za 4-pikolilamin (4); 4. uklanjanje Boc-zaštitne skupine sa spoja 4 (5);
5. sinteza spoja 2 iz L-His i heptanoil-klorida; 6. kondenzacijska reakcija spojeva 5 i 2 (6);
7. prevođenje spoja 6 u hidrokloridnu sol (7a). Ciljani spoj 7a ispitan je na mogućnost geliranja deionizirane vode i fosfatnog pufera pri čemu ne tvori hidrogel, već koloidnu otopinu, dok spojevi 7b, 7c i 7d uspješno tvore hidrogelove. Svi ispitivani spojevi pokazali su mogućnost koordinacije Zn2+, kao i katalitički učinak u hidrolitičkoj reakciji nastanka p-NP iz p-NPA, uz potrebnu dodatnu optimizaciju metode.

Abstract (english)

The aim of the study was to synthesize and characterize compound (S)-11-(2-heptanamido-3-(1H-imidazol-4-yl)propanamido)-N-(pyridin-4-ylmethyl)undecanamide hydrochloride (7a), a derivative of L-histidine (L-His), as a potential low molecular weight gelator (LMWG) of amphiphilic properties. The target compound was examined for its molecular self-assembly potential, i.e. formation of hydrogels, as well as the ability to coordinate Zn2+. Furthermore, the catalytic activity of the newly synthesized compound was investigated through the reaction of hydrolytic conversion of p-nitrophenyl acetate (p-NPA) to p-nitrophenol (p-NP), which models the process of natural ester hydrolysis reaction in biological systems. Previously synthesized compounds, structural analogues of compound 7a with altered amino acids (7b – L-phenylalanine derivative, 7c – L-phenylglycine derivative and 7d – L-tryptophan derivative) were also investigated for the possibility of forming complexes with Zn2+ and catalytic action. Measurements were carried by UV/Vis spectroscopy. Newly synthesized compound 7a contains a long aliphatic chain, amino acid
L-His and terminal 4-picolylamine. Its preparation was successfully carried out in 7 steps:
1. protection of 11-aminoundecanoic acid (AUDA) with a Boc group (1); 2. activation of compound 1 by N-hydroxysuccinimide (NHS) (3); 3. substitution of the succinimide group of compound 3 for 4-picolylamine (4); 4. removal of the Boc-protective group from compound 4 (5); 5. synthesis of compound 2 from L-His and heptanoyl-chloride; 6. condensation reaction between compounds 5 and 2 (6); 7. conversion of compound 6 into a hydrochloride salt (7a). The targeted compound 7a was evaluated for the possibility of gel formation with deionized water and phosphate buffer, whereby a colloidal solution was formed, while compounds 7b, 7c and 7d successfully form hydrogels. All tested compounds showed the possibility of Zn2+ coordination, as well as catalytic activity in the hydrolytic reaction of p-NP formation from
p-NPA, with necessary additional method optimization.

• Keywords: molekulsko samoudruživanje; amfifilni peptidi; LMWG; biokataliza
• Keywords (english): molecular self-assembly; amphiphilic peptides; LMWG; biocatalysis
• Language: croatian
• URN:NBN: urn:nbn:hr:149:355555
• 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: sveučilišni/a magistar/magistra primijenjene kemije (sveučilišni/a magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-09-01
• Created on: 2024-09-24 12:05:52