Abstract
Here we describe the synthesis, chromatographic purification, MS and NMR characterization of a new lactosyl-derivative, i.e. a lactosyl thiophenyl-substituted triazolyl-thione l-alanine (Lac-L-TTA). This amino acid–sugar conjugate was prepared by solution synthesis in analogy to the natural fructosyl-amino acids. Furthermore, we investigated the inhibition of PC-3 prostate cancer cell colony formation by this lactose derivative in comparison with the less polar fructose-based derivative, Fru-L-TTA. This let us to compare the properties of the artificial derivative, object of the present work, with the monosaccharide-based counterpart and to obtain a preliminary information on the influence of polarity on such biological activity. A significantly higher anticancer effect of Lac-L-TTA with respect to the fructose analogue emerged from our study suggesting that the anti-metastatic potential of fructosyl-amino acids can be enhanced by increasing the polarity of the compounds, for example by introducing disaccharide moieties in place of fructose.
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Acknowledgements
We thank Prof. Antonio Roviello for his precious suggestions and Mr. Leopoldo Zona for his invaluable technical assistance. We are grateful to Dr. Virginia Carbone and Dr. Rosa Anna Siciliano from Istituto di Scienze dell’Alimentazione—CNR for their contribution to the MS characterization of Lac-L-TTA. Finally, we thank Regione Campania for the research grant received for the research project “Nuovi sistemi nucleopeptidici per applicazioni diagnostiche” under the research program Legge Regionale n. 5 (annualità 2007).
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Roviello, G.N., Iannitti, R., Palumbo, R. et al. Lac-l-TTA, a novel lactose-based amino acid–sugar conjugate for anti-metastatic applications. Amino Acids 49, 1347–1353 (2017). https://doi.org/10.1007/s00726-017-2433-2
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DOI: https://doi.org/10.1007/s00726-017-2433-2