Naslov
Impact of the Histidine-Triazole and Tryptophan- Pyrene Exchange in the WHW Peptide: Cu(II) Binding, DNA/RNA Interactions and Bioactivity

Autori
Krošl Knežević, Ivona ; Jurković, Marta ; Ribičić, Karla ; Žinić, Biserka ; Majhen, Dragomira ; Božinović, Ksenija ; Piantanida, Ivo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
28HSKIKI : 28th Croatian Meeting of Chemists and Chemical Engineers and 6th Symposium Vladimir Prelog : Book of Abstracts / Rogošić, Marko - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2023, 45-45

Skup
28. hrvatski skup kemičara i kemijskih inženjera

Mjesto i datum
Rovinj, Hrvatska, 28.03.2023. - 31.03.2023

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
WHW peptide, DNA/RNA interactions, pyrene, copper binding, spectroscopy

Sažetak
Small peptides like tryptophan – histidine – tryptophan (WHW) can form complexes with transition metals, for instance copper, and those complexes are related to many biological processes. Intriguingly, Cu2+ can cleave DNA or RNA backbone under certain conditions and some peptides with tryptophan bind non-covalently to ds-DNA/RNA. That inspired us to synthesize three new peptidoids, whereby central histidine in WHW was replaced by Ala-(triazole), and two derivatives also had one tryptophan replaced with pyrene-alkyls of different lengths and flexibility. Pyrene analogues show strong fluorescence at 480-500 nm, attributed to intramolecular exciplex formation between pyrene and tryptophan. All three peptidoids bind Cu2+ in water with strong affinity, with Trp-Ala- (triazole)-Trp binding affinity comparable to the parent WHW, and the pyrene analogues even stronger. The studied peptidoids strongly bind to ds-DNA and ds-RNA, whereby their complexes with Cu2+ exhibit distinctively different interactions in comparison to metal-free analogues, particularly in stabilization of ds-DNA against thermal denaturation. The pyrene peptidoids efficiently enter living cells with no apparent cytotoxic effect, whereby their red-shifted emission compared to the parent pyrene allows intracellular confocal microscopy imaging, showing accumulation in cytoplasmic organelles. Irradiation with 350 nm light resulted in antiproliferative effect on cells treated with micromolar concentrations of the pyrene analogues, attributed to the pyrene-induced production of singlet oxygen and consecutive cellular damage.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA