Priprava i konformacijska analiza ferocenskih tripeptida Ala-Pro sekvence izvedenih iz ferocen-1,1'-diamina

master's thesis

• Title (english): Synthesis and conformational analysis of ferrocene tripeptides derived from ferrocene-1,1'-diamine and Ala-Pro sequence
• Author: Tea Stipčić
• Mentor: Monika Kovačević (mentor)
• Committee member: Lidija Barišić (predsjednik 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: 2020-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Nutrition

Abstract

Biološka primjena prirodnih peptida ograničena je njihovim nepoželjnim svojstvima (konformacijska fleksibilnost, niska stabilnost) zbog čega se intenzivno istražuje područje peptidomimetika. Ferocenski konjugati s aminokiselinama često se koriste kao peptidomimetici jer su se 1, n-disupstituirani ferocenski biokonjugati pokazali dobrim kalupom za tvorbu intramolekulskih vodikovih veza. Sekvence bogate alaninom i prolinom pokazuju brojna poželjna svojstva (visoka topljivost, stabilnost i biodostupnost), dok ferocenski diamin inducira tvorbu intramolekulskih vodikovih veza koje su stabilizirane 14-članim prstenovima. U ovom Diplomskom radu opisana je sinteza i konformacijska analiza ferocenskih tripeptida 12-15 [Ac-L(D)-Ala-D-Pro-NH-Fn-NH-L(D)-Pro-Boc, Fn = ferocenilen, Ac = acetil, Boc = tert-butoksikarbonil] kao i njihovih prekursora 2-5 [Boc(Ac)-L(D)-Ala-D-Pro-NH-Fca-COOMe], izvedenih iz ferocen-1,1'-diamina i peptidne sekvence Ala-Pro. Utjecaj kiralnosti pojedinih aminokiselina u peptidnom lancu, kao i N-terminalnih zaštitnih skupina (Boc, Ac) ispitani su spektroskopskom analizom (IR-, NMR- i CD-spektroskopija) te potkrijepljeni DFT-računima. Pokazalo se da promjenom kiralnosti aminokiselina dolazi do promjene u obrascima vodikovih veza, dok zaštitne skupine nemaju utjecaj na tvorbu istih.

Abstract (english)

The biological application of natural peptides is limited by their undesirable properties (conformational flexibility, low stability), therefore the field of peptidomimetics is being intensively investigated. As the 1, n-disubstituted ferrocene bioconjugates have been established as good motif for the formation of intramolecular hydrogen bonds, ferrocene conjugates with amino acids are often used as peptidomimetics. Regarding to that alanine- and proline-rich sequences exhibit a number of desirable properties (high solubility, stability, and bioavailability), as well as the ferrocene diamine induces the formation of intramolecular hydrogen bonds that are stabilized by forming 14-membered rings we have decided to prepare new type of peptidomimetics. This Graduate Thesis describes the synthesis and conformational analysis of ferrocene tripeptides 12-15 [Ac-L(D)-Ala-D-Pro-NH-Fn-NH-L(D)-Pro-Boc, Fn = ferrocenylene, Ac = acetyl, Boc = tert-butoxycarbonyl] as well as their precursors 2-5 [Boc(Ac)-L(D)-Ala-D-Pro-NH-Fca-COOMe], derived from ferrocene-1,1'-diamine and Ala-Pro peptide sequences. The influence of chirality of individual amino acids in the peptide chain, as well as N-terminal protecting groups (Boc, Ac) were examined by spectroscopic analysis (IR-, NMR- and CD-spectroscopy) and supported by DFT-calculations. It has been shown that change in the chirality of amino acids leads to change in the hydrogen bond patterns, while the protecting groups have no effect on their formation.

• Keywords: ferocen; sekundarna struktura; konformacijska analiza; peptidomimetici; DFT
• Keywords (english): ferrocene; secondary structure; conformational analysis; peptidomimetics; DFT
• Language: croatian
• URN:NBN: urn:nbn:hr:159:063241
• Study programme: Title: Nutrition; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra nutricionizma (magistar/magistra nutricionizma)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-07-20 12:12:21