Keywords: Nucleopeptides, Nucleic Acid Interaction, Poly(ra) Binding, Circular Dichroism, Dna Chemistry Metabolism, Microscopy, Electron, Scanning, Nucleic Acid Conformation, Peptides Chemical Synthesis Chemistry Metabolism, Rna Metabolism, Spectrophotometry, Ultraviolet, Thymine Chemistry, Beta-Alanine Analogs, Derivatives Chemistry, Alpha Peptide, Diaminopropionic Acid, Double Stranded Dna, Double Stranded Rna, Nucleic Acid Base, Polyadenylic Acid, Polynucleotide, Single Stranded Dna, Single Stranded Rna, Unclassified Drug, 3-Diaminopropionic Acid, Beta Alanine, Article, Conformational Transition, Controlled Study, Mass Spectrometry, Molecular Recognition, Nucleic Acid Structure, Nucleic Acid Synthesis, Oligomerization, Protein Dna Binding, Protein Rna Binding, Scanning Electron Microscopy, Static Electricity, Stoichiometry, Thermostability, Ultraviolet Spectroscopy, Analogs And Derivatives, Ultraviolet Spectrophotometry,
Affiliations: *** IBB - CNR ***
CNR-Institute of Biostructure and Bioimaging, Naples, Italy.
Department of Chemical Sciences, University of Naples Federico II, Naples, Italy.
Analytical Chemistry for the Environment and Centro Servizi Metereologici Avanzati, University of Naples Federico II, Naples, Italy.
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DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications
Background:
Nucleobase-bearing peptides and their interaction with DNA and RNA are an important topic in the development of therapeutic approaches. On one hand, they are highly effective for modulating the nucleic-acid-based biological processes. On the other hand, they permit to overcome some of the main factors limiting the therapeutic efficacy of natural oligonucleotides, such as their rapid degradation by nucleases.
Methods and results:
This article describes the synthesis and characterization of a novel thymine-bearing nucleoamino acid based on the l-diaminopropionic acid (l-Dap) and its solid phase oligomerization to α-peptides (oligoDapT), characterized using mass spectrometry, spectroscopic techniques, and scanning electron microscopy (SEM) analysis. The interaction of the obtained nucleopeptide with DNA and RNA model systems as both single strands (dA
12
, rA
12
, and poly(rA)) and duplex structures (dA
12
/dT
12
and poly(rA)/poly(rU)) was investigated by means of circular dichroism (CD) and ultraviolet (UV) experiments. From the analysis of our data, a clear ability of the nucleopeptide to bind nucleic acids emerged, with oligoDapT being able to form stable complexes with both unpaired and double-stranded DNA and RNA. In particular, dramatic changes in the dA
12
/dT
12
and poly(rA)/poly(rU) structures were observed as a consequence of the nucleopeptide binding. CD titrations revealed that multiple peptide units bound all the examined nucleic acid targets, with T
Ldap
/A or T
Ldap
/A:T(U) ratios >
4 in case of oligoDapT/DNA and ~2 in oligoDapT/RNA complexes.
Conclusion:
Our findings seem to indicate that Dap-based nucleopeptides are interesting nucleic acid binding-tools to be further explored with the aim to efficiently modulate DNA- and RNA-based biological processes.
DNA- and RNA-binding ability of oligoDapT, a nucleobase-decorated peptide, for biomedical applications