Impact of α-hydrazino acids embedded in short fluorescent peptides on peptide interaction with DNA and RNA

Suć, Josipa; Tumir, Lidija-Marija; Glavaš-Obrovac, Ljubica; Jukić, Marijana; Piantanida, Ivo; Jerić, Ivanka (2016) Impact of α-hydrazino acids embedded in short fluorescent peptides on peptide interaction with DNA and RNA. Organic and Biomolecular Chemistry, 14 (21). pp. 4865-4874. ISSN 1477-0520

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Official URL: http://pubs.rsc.org/en/Content/ArticleLanding/2016...

Abstract

Series of novel hydrazino-based peptidomimetics and analogues comprising N-terminal lysine and C-terminal phenanthridinyl-L-alanine were prepared. Presented results demonstrate up till now unknown possibility to finely modulate peptide interaction with DNA/RNA by α-hydrazino group insertion and how different positioning of two α-hydrazino groups in peptide 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 binding mode is combination of electrostatic interactions and hydrophobic interactions within DNA/RNA grooves. Insertion of α-hydrazino group into peptide systematically decreased its fluorimetric response to DNA/RNA binding in line: mono-hydrazino<alternating-hydrazino<sequential-hydrazino group. Binding studies to ss-polynucleotides suggest intercalation of phenanthridine between polynucleotide bases, whereby affinity and fluorimetric response decrease with the number of α-hydrazino groups in peptide sequence. Particularly interesting was interaction of two sequential α-hydrazino acids-peptidomimetic with poly rG, characterised by specific strong increase of CD bands, while all other peptide/ssRNA combinations gave only CD-bands decrease. All mentioned interactions could also be reversibly controlled by pH, due to the protonation of the fluorophore.

Item Type:

Article

Additional Information:

This work has been supported by Croatian Science Foundation projects 1477 and 3102. The support from FP7-REGPOT-2012-2013-1 project, Grant Agreement Number 316289 – InnoMol is gratefully acknowledged.

Uncontrolled Keywords:

hydrazino; peptidomimetic; DNA/RNA; interactions

Subjects:

NATURAL SCIENCES > Chemistry
NATURAL SCIENCES > Chemistry > Organic Chemistry

Divisions:

Division of Organic Chemistry and Biochemistry

Projects:

Project title	Project leader	Project code	Project type
Višekomponentne reakcije u sintezi peptidnih mimetika-MIMICRy	IVANKA JERIĆ	IP-09-2014-3102	HRZZ
Višenamjensko očitavanje DNA / RNA sekundarne strukture molekularnim kemijskim senzorima-DNA/RNA-MolSense	Ivo Piantanida	IP-11-2013-1477	HRZZ
FP7-REGPOT-2012-2013-1 project Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development-INNOMOL	UNSPECIFIED	316289	EK