Sinteza in pretvorbe Nα-benziloksikarbonil-Nβ-terc-butoksikarbonil-3,7-diamino-1-diazo-2-oksoheptana

Lipovec, Doroteja (avtor), Svete, Jurij (mentor)

Biološke sonde oziroma 'acivity-based probes' so male molekule, ki se ireverzibilno vežejo na aktivno mesto proteaze. Vsebujejo reaktivno elektrofilno skupino ("bojno glavo"), ki reagira z aktivnim mestom preiskovanega encima, in označevalec; povezuje pa ju distančnik, ki z ustreznim aminokislinskim zaporedjem poveča selektivnost sonde. Diazoketon (Nα-benziloksikarbonil-Nβ-terc-butoksikarbonil-3,7-diamino-1-diazo-2-oksoheptan) smo sintetizirali iz Z-Lys(Boc)-OH po že znanem postopku iz literature. Iz diazoketona smo sintetizirali aciloksimetil keton (AOMK) (Nα-benziloksikarbonil-Nβ-terc-butoksikarbonil-3,7-diamino-2-oksoheptil 2,6-dimetilbenzoat) po različnih poteh. AOMK smo najprej sintetizirali z direktno sintezo med diazoketonom in 2,6-dimetilbenzojsko kislino v fluoriranem alkoholu (TFE). Zatem smo AOMK želeli sintetizirati preko p-tozilatnega derivata, ki pa je razpadel, zato je bila sinteza neuspešna. AOMK smo nato sintetizirali preko klorometil ketona po modificiranem postopku iz literature.

• Jezik: Slovenski jezik
• Ključne besede: biološke sonde, elektrofilne bojne glave, aciloksimetil ketoni, diazoketoni, kaspaze
• Vrsta gradiva: Diplomsko delo/naloga
• Tipologija: 2.11 - Diplomsko delo
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Leto izida: 2022
• PID: 20.500.12556/RUL-140013
• COBISS.SI-ID: 128970755
• Datum objave v RUL: 09.09.2022

LIPOVEC, Doroteja, 2022, Sinteza in pretvorbe Nα-benziloksikarbonil-Nβ-terc-butoksikarbonil-3,7-diamino-1-diazo-2-oksoheptana [na spletu]. Diplomsko delo. [Dostopano 19 maj 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=140013

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Synthesis and transformation of Nα-benzyloxycarbonyl-Nβ-tert-butoxycarbonyl-3,7-diamino-1-diazo-2-oxoheptane

Izvleček

Activity-based probes are small molecules that bind specifically and irreversibly to active proteases. They consist of a reactive functional group (“electrophilic warhead”) that binds to the active site of the target enzyme, a tag that enables enzyme detection, and a linker that is a peptide based sequence that connects the warhead with the tag and provides the selectivity towards an enzyme of interest. Diazoketone (Nα-benzyloxycarbonyl-Nβ-tert-butoxycarbonyl-3,7-diamino-1-diazo-2-oxoheptane) was synthesized from Z-Lys(Boc)-OH following a procedure described in the literature. Acyloxymethyl ketone (AOMK) (Nα-benzyloxycarbonyl-Nβ-tert-butoxycarbonyl-3,7-diamino-2-oxoheptyl 2,6-dimethylbenzoate) was then synthesized from the diazoketone using different methods. AOMK was first synthesized via direct substitution reaction between the diazoketone and 2,6-dimethylbenzoic acid in a fluorinated solvent (TFE). Synthesis of AOMK through the p-tosylate derivative was unsuccessful as the derivative decomposed. AOMK was then synthesized through a chloromethyl ketone according to a modified literature procedure.

• Ključne besede: activity-based probes, electrophilic warheads, acyloxymethyl ketones, diazoketones, caspases