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Guanidiniocarbonyl-pyrrole-aryl derivatives : structure tuning for spectrophotometric recognition of specific DNA and RNA sequences and antiproliferative activity

Hernandez-Folgado, Laura; Baretić, Domagoj; Piantanida, Ivo; Marjanović, Marko; Kralj, Marijeta; Rehm, Thomas; Schmuck, Carsten (2010) Guanidiniocarbonyl-pyrrole-aryl derivatives : structure tuning for spectrophotometric recognition of specific DNA and RNA sequences and antiproliferative activity. Chemistry : a European journal, 16 (10). pp. 3036-3056. ISSN 0947-6539

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Abstract

We present here a systematic study of different guanidiniocarbonyl-pyrrole-aryl derivatives designed to interact with DNA or RNA both by intercalation of an aromatic moiety into the base stack of the nucleotide as well as groove binding of a guanidinio-carbonyl pyrrole cation. We varied 1.) the size of the aromatic ring (benzene, naphthalene, pyrene and acridine), 2.) the length and flexibility of the linker connecting the two binding groups, as well as 3.) the total number of positive charges present at different pH values. The compounds and their interaction with DNA and RNA were studied by UV/Vis-, fluorescence and CD spectroscopy. Also the antiproliferative activity against human tumour cell lines was determined. Our studies show that efficient interaction with e.g. DNA requires a significantly large aromatic ring (pyrene) connected via a flexible linker to the pyrrole moiety. However, a positive charge as in 12 is also needed. Compound 12 allows for a base pair selective recognition of ds-DNA at physiological pH. The antiproliferative activity correlates with the binding affinity of these compounds towards DNA suggesting that the biological effect is most likely due to DNA binding.

Item Type: Article
Uncontrolled Keywords: DNA/RNA binding; intercalation; molecular recognition; antiproliferation
Subjects: NATURAL SCIENCES > Chemistry
Divisions: Division of Molecular Medicine
Division of Organic Chemistry and Biochemistry
Projects:
Project titleProject leaderProject codeProject type
Dizajn, sinteza i ispitivanje interakcija malih molekula s DNA, RNA i proteinima-Ivo Piantanida098-0982914-2918MZOS
Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA-Marijeta Kralj098-0982464-2514MZOS
Depositing User: Ivo Piantanida
Date Deposited: 20 Dec 2016 14:24
Last Modified: 20 Dec 2016 14:24
URI: http://fulir.irb.hr/id/eprint/1618
DOI: 10.1002/chem.200901999

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