title: The impact of α-hydrazino acids embedded in short fluorescent peptides on peptide interactions with DNA and RNA.
abstract: A series of novel hydrazino-based peptidomimetics and analogues comprising N-terminal lysine and C-terminal phenanthridinyl-l-alanine were prepared. The presented results demonstrate the up to now unknown possibility to finely modulate peptide interactions with DNA/RNA by α-hydrazino group insertion and how the different positioning of two α-hydrazino groups in peptides controls binding to various double stranded and single stranded DNA and RNA. All peptidomimetics bind with 1-10 micromolar affinity to ds-DNA/RNA, whereby the binding mode is a combination of electrostatic interactions and hydrophobic interactions within DNA/RNA grooves. Insertion of the α-hydrazino group into the peptide systematically decreased its fluorimetric response to DNA/RNA binding in the order: mono-hydrazino < alternating-hydrazino < sequential-hydrazino group. Binding studies of ss-polynucleotides suggest intercalation of phenanthridine between polynucleotide bases, whereby affinity and fluorimetric response decrease with the number of α-hydrazino groups in the peptide sequence. Particularly interesting was the interaction of two sequential α-hydrazino acids-peptidomimetic with poly rG, characterised by a specific strong increase of CD bands, while all other peptide/ssRNA combinations gave only a CD-band decrease. All mentioned interactions could also be reversibly controlled by adjusting the pH, due to the protonation of the fluorophore.
authors.affiliation: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia. pianta@irb.hr ijeric@irb.hr.
authors.forename: Josipa
authors.initials: J
authors.lastname: Suć
authors.forename: Lidija-Marija
authors.initials: LM
authors.lastname: Tumir
authors.forename: Ljubica
authors.initials: L
authors.lastname: Glavaš-Obrovac
authors.forename: Marijana
authors.initials: M
authors.lastname: Jukić
authors.forename: Ivo
authors.initials: I
authors.lastname: Piantanida
authors.forename: Ivanka
authors.initials: I
authors.lastname: Jerić
mesh_terms: D000818:Animals; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism*; D006834:Hydrazines / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D057786:Peptidomimetics / Q000737:chemistry* / Q000378:metabolism*; D012313:RNA / Q000737:chemistry / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D006834:Hydrazines; D057786:Peptidomimetics; C029424:hydrazine; D012313:RNA; D004247:DNA