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Novel insights into nucleoamino acids: biomolecular recognition and aggregation studies of a thymine-conjugated l-phenyl alanine

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Abstract

This article deals with the synthesis in solid phase and characterization of a nucleoamino amide, based on a phenylalaninamide moiety which was N-conjugated to a thymine nucleobase. In analogy to the natural nucleobase–amino acid conjugates, endowed with a wide range of biological properties, the nucleoamino amide interacts with single-stranded nucleic acids as verified in DNA- and RNA-binding assays conducted by CD and UV spectroscopies. These technologies were used to show also that this conjugate binds serum proteins altering significantly their secondary structure, as evidenced by CD and UV using BSA as a model. The biomolecular recognition seems to rely on the ability of the novel compound to bind aromatic and heteroaromatic moieties in protein and nucleic acids, not hindered by its propensity to self-assemble in aqueous solution, behavior suggested by dynamic light scattering (DLS) and CD spectroscopy in concentration- and temperature-dependent experiments. Finally, the high stability in human serum concurs to define the picture of the nucleoamino amide: this enzymatically stable drug candidate could interfere with protein and single-stranded nucleic acid-driven biological processes, particularly those associated with mRNA poly(A) tail, and its self-assembling nature, in analogy to other l-Phe-based systems, discloses new scenarios in drug delivery technology.

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Acknowledgements

I thank Prof. Antonio Roviello for his precious suggestions and Mr. Leopoldo Zona for his invaluable technical assistance.

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  1. Istituto di Biostrutture e Bioimmagini-CNR (UOS Napoli centro), 80134, Naples, Italy

    Giovanni N. Roviello

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  1. Giovanni N. Roviello
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Correspondence to Giovanni N. Roviello.

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Handling Editor: F. Albericio.

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726_2018_2562_MOESM1_ESM.doc

An abbreviation list and the description of materials and methods, together with the copies of 1H and 13C NMR spectra, two energy-minimized 3D molecular views and some predicted properties of L-PheT are reported in this section

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Roviello, G.N. Novel insights into nucleoamino acids: biomolecular recognition and aggregation studies of a thymine-conjugated l-phenyl alanine. Amino Acids 50, 933–941 (2018). https://doi.org/10.1007/s00726-018-2562-2

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  • DOI: https://doi.org/10.1007/s00726-018-2562-2

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