Modeliranje sinteze farmaceutika katalizirane imobiliziranim enzimom

master's thesis

• Title (english): Modelling of pharmaceutical synthesis catalysed by immobilized enzyme
• Author: Stella Hamilton
• Mentor: Ana Vrsalović Presečki (mentor)
• Committee member: Ana Vrsalović Presečki (predsjednik povjerenstva)
• Committee member: Ana Lončarić Božić (član povjerenstva)
• Committee member: Vanja Kosar (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2022-02-25, Croatia
• Scientific / art field, discipline and subdiscipline: TECHNICAL SCIENCES; Chemical Engineering

Abstract

Statini su farmaceutici koji se koriste pri snižavanju kolesterola te sprečavanju pojave kardiovaskularnih bolesti. Sve je veća potražnja za novim alternativnim načinima dobivanja kemikalija s kiralnim centrima čija je sinteza kompleksna zbog potrebe za visokom kemijskom i stereokemijskom čistoćom, a upravo jedan od njih je uporaba enzima 2-deoksiriboze-5-fosfat aldolaze (DERA). DERA katalizira reakciju sinteze (3R, 5R)-6-kloro-3,5-dihidroksiheksanala (laktola), prekursora u proizvodnji statina, dvostrukom aldolnom adicijom acetaldehida i kloroacetaldehida. U radu, imobiliziran je enzim DERA na magnetske nanočestice obložene silikom u svrhu povećanja stabilnosti enzima u prisustvu aldehida. Ispitani su utjecaji različitih pH vrijednosti 0,1 M fosfatnog pufera na aktivnost i stabilnost enzima DERA gdje se kao optimalna pH vrijednost pokazao pH 6 u kojem je enzim pokazao najveću aktivnost i stabilnost. U reakciji acetaldehida i kloroacetaldehida te u reakciji acetaldehida i 4-kloro-3-hidroksibutanala kinetika je opisana dvosupstratnom Michaelis-Menteničinom jednadžbom te je postavljen matematički model procesa u kotlastom reaktoru. Ispitana je stabilnost enzima u prisutnosti različitih koncentracija acetaldehida i kloroacetaldehida.

Abstract (english)

Statins are pharmaceuticals used to lower cholesterol and prevent cardiovascular disease. There is a growing demand for new alternative ways to obtain chemicals with chiral centers, whose synthesis is complex due to the need for high chemical and stereochemical purity. One of the possibility is the use of the enzyme 2-deoxyribose-5-phosphate aldolase (DERA). DERA catalyzes the synthesis reaction of (3R, 5R)-6-chloro-3,5-dihydroxyhexanal (lactol), a precursor in statin production, by double aldol addition of acetaldehyde and chloroacetaldehyde. The DERA enzyme was immobilized on magnetic nanoparticles coated with silica to enhance the stability of the enzyme in the presence of aldehydes. The effects of different pH values of 0.1 M phosphate buffer on the activity and stability of DERA were investigated, and pH 6 was found to be the optimal pH with respect to the enzyme activity and stability. In the reaction of acetaldehyde and chloroacetaldehyde and in the reaction of acetaldehyde and 4-chloro-3-hydroxybutanal, the kinetics was described by the two-substrate Michaelis-Menten equation and a mathematical model of the process in the batch reactor was set. Enzyme stability was examined in the presence of different concentrations of acetaldehyde and chloroacetaldehyde.

• Keywords: statini; enzim; deoksiriboza-5-fosfat aldolaza; DERA; imobilizacija enzima; magnetske nanočestice; kinetika; deaktivacija enzima
• Keywords (english): statins; enzyme; deoxyribose-5-phosphate aldolase; DERA; enzyme immobilization; magnetic nanoparticles; kinetics; enzyme deactivation
• Language: croatian
• URN:NBN: urn:nbn:hr:149:347005
• Study programme: Title: Environmental Engineering - Graduate study; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka ekoinženjerstva (magistar/magistra inženjer/inženjerka ekoinženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-03-01
• Created on: 2023-03-09 14:19:43