Synthesis and photochemistry of oligopeptides functionalized by quinone methide precursor and their binding to polynucleotides

Glavaš, Mladena; Sviben, Igor; Erben, Antonija; Bachelart, Thomas; Karakaš, Antonija; Germain, Morgan; Piantanida, Ivo; Basarić, Nikola Synthesis and photochemistry of oligopeptides functionalized by quinone methide precursor and their binding to polynucleotides. In: The 26th Polish Peptide Symposium (3 September 2023 - 7 September 2023) Stare Jabłonki, Poljska. (Unpublished)

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Abstract

Binding of peptides to polynucleotides (DNA) is an important biological process, which can regulate translation and transcription, and therefore, it enables applications in biology, medicine and biochemistry [1]. DNA-binding oligopeptides can be easily functionalized by fluorophores [2] and by DNA cross-linking agents (inducing DNA-peptide cross-links) [3]. Molecules that have been intensively investigated as DNA cross-linking agents are quinone methides (QMs) [4a]. This group of compounds are reactive intermediates in the phenol chemistry and photochemistry, which can be generated in photochemical reactions under mild conditions [4]. They are highly reactive species that react with a variety of biological nucleophiles [5]. However, for efficient DNA alkylation, it is important to attach the QM precursor group noncovalently to DNA prior to its generation [6]. Herein we present the synthesis of new oligopeptides 1 – 3 containing QM precursor in the modified amino acid tyrosine (Scheme 1), whereas binding to polynucleotides is anticipated owing to incorporation of pyrene (Pyr) or bis-arginine. The synthesis started from Boc-protected amino acid lysine, β-amino alanine or arginine. Dipeptides 1 and 2 were prepared through three steps, while tripeptide 3 was prepared through six steps, where the last two steps are condensation with modified tyrosine and deprotection, for all three oligopeptides. The photochemical reactivity was investigated by irradiations in nucleophilic solvents whereupon photosolvolysis products indicate QM generation. Photophysical properties of 1 – 3, and their binding to polynucleotides were investigated by spectroscopic techniques (UV/Vis, fluorescence spectroscopy and circular dichroism).

Item Type:

Unpublished conference/workshop items or lecture materials

Uncontrolled Keywords:

peptides; polynucleotides; quinone methides; oligopeptides; DNA

Subjects:

NATURAL SCIENCES > Chemistry > Analytic Chemistry
NATURAL SCIENCES > Chemistry > Organic Chemistry

Divisions:

Division of Organic Chemistry and Biochemistry
NMR Center

Projects: