Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides

Matić, Josipa; Piotrowski, Patryciusz; Vrban, Lucija; Kobetić, Renata; Vianello, Robert; Jurić, Ivona; Fabijanić, Ivana; Pernar Kovač, Margareta; Brozović, Anamaria; Piantanida, Ivo; Schmuck, Carsten; Radić Stojković, Marijana (2024) Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides. International Journal of Molecular Sciences, 25 (9). ISSN 1422-0067

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Abstract

Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter’s crucial influence on successful polynucleotide recognition. Substituting one glycine with lysine in two regioisomers (22, 23) resulted in stronger binding interactions with DNA and RNA than for a compound containing two glycines (19), thus emphasizing the importance of lysine. The regioisomer with lysine closer to the phenanthridine ring (23) exhibited a dual and selective fluorimetric response with non-alternating AT and ATT polynucleotides and induction of triplex formation from the AT duplex. The best binding constant (K) with a value of 2.5 × 107 M−1 was obtained for the interaction with AT and ATT polynucleotides. Furthermore, apart from distinguishing between different types of ds-DNA and ds-RNA, the same compound could recognize GC-rich DNA through distinct induced CD signals.

Item Type:	Article
Uncontrolled Keywords:	DNA/RNA recognition ; phenanthridine peptides ; spectrophotometric AT- and GC-base pair probe ; molecular dynamics simulations
Subjects:	NATURAL SCIENCES > Chemistry NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Biology Division of Organic Chemistry and Biochemistry
Projects:	Project title Project leader Project code Project type Molekularno prepoznavanje DNA:RNA hibridnih i višelančanih struktura u bioanalitičkim i in vitro sustavima-DNARNAHyB-MolBio Marijana Radić Stojković IP-2018-01-4694 HRZZ Višenamjensko očitavanje DNA/RNA sekundarne strukture molekularnim kemijskim senzorima-DNA/RNA-MolSense Ivo Piantanida; Carsten Schmuck; Tamara Šmidlehner IP-2013-11-1477 HRZZ
Depositing User:	Ana Zečević
Date Deposited:	22 Jul 2024 10:35
URI:	http://fulir.irb.hr/id/eprint/8960
DOI:	10.3390/ijms25094866

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