Synthesis and nucleic acid binding evaluation of a thyminyl L-diaminobutanoic acid-based nucleopeptide

Musumeci D, Mokhir A, Roviello GN (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Bioorganic Chemistry Elsevier

Book Volume: 100

Article Number: 103862

DOI: 10.1016/j.bioorg.2020.103862

Abstract

Herein we present the synthesis of a L-diaminobutanoic acid (DABA)-based nucleopeptide (3), with an oligocationic backbone, realized by solid phase peptide synthesis using thymine-bearing DABA moieties alternating in the sequence with free ones. CD studies evidenced the ability of this oligothymine nucleopeptide, well soluble in aqueous solution, to alter the secondary structure particularly of complementary RNA (poly rA vs poly rU) and inosine-rich RNAs, like poly rI and poly rIC, and showed its preference in binding double vs single-stranded DNAs. Furthermore, ESI mass spectrometry revealed that 3 bound also G-quadruplex (G4) DNAs, with either parallel or antiparallel topologies (adopted in our experimental conditions by c-myc and tel22, respectively). However, it caused detectable changes only in the CD of c-myc (whose parallel G4 structure was also thermally stabilized by ~3 °C), while leaving unaltered the antiparallel structure of tel22. Interestingly, CD and UV analyses suggested that 3 induced a hybrid mixed parallel/antiparallel G4 DNA structure in a random-coil tel22 DNA obtained under salt-free buffer conditions. Titration of the random-coil telomeric DNA with 3 gave quantitative information on the stoichiometry of the obtained complex. Overall, the findings of this work suggest that DABA-based nucleopeptides are synthetic nucleic acid analogues potentially useful in antigene and antisense strategies. Nevertheless, the hexathymine DABA-nucleopeptide shows an interesting behaviour as molecular tool per se thanks to its efficacy in provoking G4 induction in random coil G-rich DNA, as well as for the possibility to bind and stabilize c-myc oncogene in a G4 structure.

Authors with CRIS profile

Andriy Mokhir Professur für Organische Chemie

Involved external institutions

Università degli Studi di Napoli Federico II IT Italy (IT) Institute of Biostructure and Bioimaging (IBB) / Istituto di Biostrutture e Bioimmagini IT Italy (IT)

How to cite

APA:

Musumeci, D., Mokhir, A., & Roviello, G.N. (2020). Synthesis and nucleic acid binding evaluation of a thyminyl L-diaminobutanoic acid-based nucleopeptide. Bioorganic Chemistry, 100. https://doi.org/10.1016/j.bioorg.2020.103862

MLA:

Musumeci, Domenica, Andriy Mokhir, and Giovanni N. Roviello. "Synthesis and nucleic acid binding evaluation of a thyminyl L-diaminobutanoic acid-based nucleopeptide." Bioorganic Chemistry 100 (2020).

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