Interakcije 9a-aminopropil derivata azitromicina i ribosoma izoliranog iz bakterije Esherichia coli

master's thesis

• Title (english): Interactions of 9a-aminopropyl derivate of azithromycin and ribosome isolated from the bacteria Escherichia coli
• Author: Iva Kušec
• Mentor: Predrag Novak (mentor)
• Committee member: Predrag Novak (predsjednik povjerenstva)
• Committee member: Ivana Biljan (član povjerenstva)
• Committee member: Jasmina Rokov Plavec (član povjerenstva)
• Committee member: Tomislav Jednačak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2021-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Makrolidni antibiotici koriste se u posljednjih 60 godina najčešće za liječenje infekcija gornjih
i donjih dišnih puteva. Djelovanje makrolidnih antibiotika temelji se na inhibiciji sinteze
bakterijskih proteina vezanjem antibiotika na 50S podjedinicu bakterijskog ribosoma.
Povećanje bakterijske rezistencije na postojeće makrolidne antibiotike dovelo je do potrebe za
otkrićem i razvojem novih antibiotika. Za potpuno razumijevanje bioaktivnosti makrolidnog
antibiotika, potrebno je odrediti konformacije u slobodnom i vezanom stanju te istražiti
interakcije s bakterijskim ribosomom. U ovom radu okarakteriziran je 9a-aminopropil derivat
azitromicina, prekursor u sintezi makrozona, pomoću jedno- i dvodimenzijskih tehnika NMR.
Makrozoni su konjugati azitromicina i tiosemikarbazona. Pomoću tehnike NOESY određena je
konformacija prekursora u slobodnom stanju. Konformacija prekursora u vezanom stanju
određena je pomoću tehnike trNOESY, dok su interakcije prekursora s ribosomom izoliranim
iz bakterije Escherichia coli istražene pomoću tehnike STD.

Abstract (english)

Macrolide antibiotics have been used over the past 60 years, to treat upper and lower respiratory
tract infections. Macrolides inhibit bacterial protein synthesis by binding to the 50S subunit of
the bacterial ribosome. Increasing bacterial resistance to existing macrolide antibiotics has
speed up the process of discovery of new antibiotics. To fully understand bioactivity of
macrolide antibiotics, it is necessary to determine structure and conformation in the free and
bound states and to investigate the interactions with the bacterial ribosome. In this paper, the
structure of 9a-aminopropyl derivative of azithromycin, a precursor in the synthesis of the
corresponding macrozone, was characterized by using one- and two-dimensional NMR
spectroscopy. Macrozones are conjugates of azithromycin and thiosemicarbazones. The
conformation of the precursor in the free and bound states was determined by NOESY and
transferred NOESY spectral analysis, while the interactions with the ribosome isolated from
Escherichia coli were investigated using the STD technique.

• Keywords: azitromicin; interakcije; makrolidni antibiotici; makrozoni; ribosom; spektroskopija NMR; tehnika NOESY; tehnika STD
• Keywords (english): azithromycin; interactions; macrolide antibiotics; macrozone; NMR spectroscopy; NOESY technique; ribosome; STD technique
• Language: croatian
• URN:NBN: urn:nbn:hr:217:529671
• Project: Number: IP-2018-01-8098; Title: Makrozoni, novi konjugati makrolidnih antibiotika: Dizajn, priprava i interakcije; Title: Macrozones, New Conjugates of Macrolide Antibiotics: Design, Synthesis and Interactions; Acronym: Makrozoni/Macrozones; Leader: Predrag Novak; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• 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
• Created on: 2021-10-15 12:01:24