Priprava i konformacijska analiza enantiomernih ferocenskih depsipeptida s fenilalaninom

master's thesis

• Title (english): Preparation and conformational analysis of enantiomeric ferrocene depsipeptides with phenylalanine
• Author: Vita Vučičević
• Mentor: Monika Kovačević (mentor)
• Committee member: Lidija Barišić (predsjednik povjerenstva)
• Committee member: Mojca Čakić Semenčić (član povjerenstva)
• Committee member: Anita Horvatić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Organic Chemistry); Zagreb
• Defense date and country: 2025-01-24, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Iako sudjeluju u izrazito važnim fiziološkim mehanizmima i kontroliraju gotovo sve vitalne funkcije u organizmu, peptidi nisu pogodi za primjenu u terapeutske svrhe, pa se različitim peptidomimetičkim modifikacijama nastoji prevladati njihova postojeća ograničenja. Umetanjem ferocenske osnove u različito strukturirane peptidne lance dolazi do formiranja intramolekulskih vodikovih veza koje uzrokuju nastajanje različitih sekundarnih strukturnih elemenata. Jedna od neistraženih modifikacija ferocenskih peptida jest zamjena jedne amidne veze esterskom vezom u svrhu priprave nove vrste peptidomimetika koji se nazivaju depsipeptidi. Prirodni depsipeptidi pokazuju širok spektar bioloških aktivnosti te predstavljaju potentne spojeve u razvoju novih sintetskih lijekova. Esterske veze uvode se u sintetičke depsipeptide s ciljem postizanja konformacijskih promjena koje utječu na karakter vodikovih veza i fleksibilnost. vodikovih Osnovni cilj ovog rada je istražiti utjecaj zamjene jedne amidne veze esterskom vezom na obrazac veza i konformacijski Ac−L−Phe−NH−Fn−CO−O−CH₂−CH[CH₂Ph]−NHBoc prostor (13) i pripravljenih depsipeptida Ac−D−Phe−NH−Fn−CO−O−CH₂− CH[CH₂Ph]−NHBoc (14). U tu svrhu dva pripravljena ciljna depsipeptida te prije sintetizirani analogni spojevi konformacijski su analizirani i uspoređeni spektroskopskim metodama (IR- , NMR- i CDspektroskopija).

Abstract (english)

Although they are involved in extremely important physiological mechanisms and control almost all vital functions in the body, peptides are not suitable for use for therapeutic purposes for several reasons. Therefore, various peptidomimetic modifications are applied to overcome the existing limitations of peptides.The insertion of a ferrocene base into differently structured peptide chains leads to the formation of intramolecular hydrogen bonds, which cause the formation of various secondary structural elements. One of the unexplored modifications of ferrocene peptides is the replacement of an amide bond by an ester bond to produce a new type of peptidomimetics, the depsipeptides. Natural depsipeptides exhibit a broad spectrum of biological activities and are leading compounds in the development of new synthetic drugs. In synthetic depsipeptides, ester bonds are introduced to achieve conformational changes that influence the character of hydrogen bonds and flexibility. The main objective of this work is to investigate the influence of the replacement of an amide bond by an ester bond on the pattern of hydrogen bonds and the conformational space of the prepared depsipeptides Ac−L−Phe−NH−Fn−CO−O−CH₂−CH[CH₂Ph]−NHBoc (13) and Ac−D−Phe−NH−Fn− CO−O−CH₂−CH[CH₂Ph]−NHBoc (14). For this purpose, two specifically prepared depsipeptides and previously synthesized analogous compounds were investigated by conformational analysis and compared using spectroscopic methods (IR, NMR and CD spectroscopy).

• Keywords: ferocen; depsipeptidi; peptidomimetici; fenilalanin; konformacijska analiza
• Keywords (english): ferrocene; depsipeptides; peptidomimetics; phenylalanine; conformational analysis
• Language: croatian
• URN:NBN: urn:nbn:hr:159:983615
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-01-28 13:52:49