Synthesis and photochemistry of oligopeptides and their potential application in diagnostics and therapy

Erben, Antonija (2024) Synthesis and photochemistry of oligopeptides and their potential application in diagnostics and therapy. Doctoral thesis, Sveučilište u Rijeci, Fakultet biotehnologije i razvoja lijekova.

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Abstract

Peptides are promising drug candidates and their further development and research is important for pharmaceutical and medicinal applications. However, peptides have some limitations due to short half-life in vivo and fast clearance from the circulation by the liver and kidneys. One way/possibility to sovle these obstacles is by incorporation of unnatural amino acids, which enzymes cannot recognize. This PhD thesis describes the preparation of an unnatural amino acid, a tyrosine derivative, which in the photochemical reaction generates reactive intermediate quinone methide. The unnatural amino acid was incorporated into oligopeptides containing bis-tryptophane unit, phenanthridine or pyrene. The synthetic protocol for the preparation of oligopeptides was based on the standard peptide activation protocols in solution and Boc protective groups. The photochemical reactivity of the oligopeptides was investigated, and the quinone methides were detected by laser flash photolysis. The photophysical properties (molar absorption coefficient, quantum yield of fluorescence and singlet excited state lifetime) of the oligopeptides were investigated, which is important for their potential diagnostic applications, as well as for the investigation of noncovalent binding to polynucleotides. The stability constants of the peptide-polynucleotide complexes were determined by fluorescence titrations, and the effect of the compounds on the thermal denaturation was investigated. The binding modes to polynucleotides were probed by CD spectroscopy. The ability of the peptides to covalently bind to oligonucleotides and polynucleotides was examined by irradiating their complexes and detecting adducts by various spectroscopic and chromatographic techniques.

Item Type:

Thesis (Doctoral thesis)

Uncontrolled Keywords:

unnatural amino acids; oligopeptides; quinone methides; photochemistry; noncovalent and covalent binding to polynucleotides

Subjects:

INTERDISCIPLINARY AREAS OF KNOWLEDGE > Biotechnology in Biomedicine (natural science, biomedicine and healthcare, bioethics area

Divisions:

Division of Organic Chemistry and Biochemistry

Projects: