Biokonjugati ferocenske aminokiseline s dipeptidom Pro-Ala: sinteza i konformacijska analiza

undergraduate thesis

• Title (english): Bioconjugates of ferroceneaminoacid with dipeptide Pro Ala: synthesis and conformational analysis
• Author: Marina Ivančić
• Mentor: Lidija Barišić (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Organic Chemistry); Zagreb
• Defense date and country: 2019-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Food Technology

Abstract

Najveći izazov u peptidomimetici predstavlja modifikacija strukture prirodnih peptida i dizajn odgovarajućih peptidomimetika s ciljem unapređenja njihovog biološkog učinka i prevladavanja ograničenosti terapeutske primjene. U ovom radu opisana je sinteza i konformacijska analiza tripeptida Boc-L-Pro-L-Ala-NH-Fn-COOMe (Fn = 1,1'-ferocenilen), nastalog kopuliranjem 1'-aminoferocen-1-karboksilne kiseline (Fca) s homokiralnom Pro-Ala sekvencom. Cilj rada bio je ispitati utjecaj slijeda, kiralnosti i bočnog ogranka prirodnih aminokiselina (Pro i Ala) kao i potencijal Fca u indukciji elemenata sekundarne peptidne strukture. Sintetizirani tripeptid podvrgnut je strukturnoj analizi primjenom IR-, NMR- (ovisnim o koncentraciji, temperaturi i otapalu) i CD- spektroskopije, u svrhu utvrđivanja njegovog konformacijskog prostora koji je ključan za potencijalni farmakološki učinak. Prema rezultatima analize, osobitost pripravljenog biokonjugata jest dominacija intramolekulskih vodikovih veza srednje jakosti koje doprinose stabilizaciji molekule, odnosno induciraju tvorbu 7- članih i 10-članih IHB-prstenova (IHB, engl. Intramolecular Hydrogen Bond), odnosno γ-i β-okreta u peptidnom lancu.

Abstract (english)

The greatest challenge in the field of peptidomimetic chemistry is the modification of the structure of natural peptides and the design of appropriate peptidomimetics with the aim of enhancing their biological effect and overcoming the limitation of therapeutic application. This study has explored the synthesis and conformational analysis of Boc-L-Pro-L-Ala-NH-Fn-COOMe (Fn = 1,1'-ferrocenilene) tripeptide obtained by copulation of 1'-aminoferrocene-1-carboxylic acid (Fca) with homochiral Pro – Ala sequence. The main goal of this study was to explore the influence of the sequence, chirality and side chain of natural amino acids (Pro and Ala) as well as the potential of Fca in the induction of secondary peptide structure elements. The synthesized tripeptide was subjected to detail structural analysis by IR, NMR (concentration-, temperature- and solvent-dependent) and CD spectroscopy in order to determine its conformational space, which has a crucial impact on potential pharmacological effect. The obtained spectroscopic results revealed the predominance of intramolecular hydrogen bonds of medium strength that contribute to the stabilization of the compound by inducing the formation of 7- and 10-membered IHB-rings (IHB, Intramolecular Hydrogen Bond), i.e. γ- and β-turns within the peptide chain.

• Keywords: intramolekulska vodikova veza; konformacijska analiza; ferocen; peptidomimetici; okret
• Keywords (english): IHB; conformational analysis; ferrocene; peptidomimetics; turns
• Language: croatian
• URN:NBN: urn:nbn:hr:159:942498
• Study programme: Title: Food Technology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka prehrambene tehnologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka prehrambene tehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2019-07-17 11:38:21