Solid phase synthesis and RNA-binding studies of a serum-resistant nucleo-ε-peptide

• Published in: Journal of peptide science Vol. 15; no. 3; pp. 155 - 160
• Main Authors: Roviello, G. N., Musumeci, D., Castiglione, M., Bucci, E. M., Pedone, C., Benedetti, E.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2009
• Subjects: Amino Acids - chemistry; Fluorenes - chemistry; Lysine - chemistry; Molecular Structure; nucleo-ε-peptides; Peptide Nucleic Acids - chemical synthesis; Peptide Nucleic Acids - chemistry; Peptide Nucleic Acids - metabolism; Polylysine - chemistry; Protein Binding; RNA - metabolism; RNA analogue; ε-lysPNA
• DOI: 10.1002/psc.1072
• ISSN: 1075-2617

In the present work we report the synthesis of a new Fmoc‐protected L‐lysine‐based nucleo‐amino acid suitable for the solid phase assembly and its oligomerisation to the corresponding nucleo‐ε‐peptide that we called ε‐lysPNA. The ability to bind complementary RNA and the stability in serum of this synthetic nucleo‐ε‐peptide were studied to explore its possible use in antisense or diagnostic applications. Our interest to the presented oligonucleotide analogue was also supported by the importance of ε‐peptides and other ε‐amino acid‐containing compounds in natural products with biological activity such as the poly‐ε‐lysines produced by Streptomyces albulus that possess a highly selective antimicrobial activity. Another aspect we intended to evaluate by this work is the possible prebiotic implication of these nucleopeptides, since ε‐peptides, and not α‐peptides, were mainly obtained among the other thermal prebiotic polypeptides in pyrocondensation of lysine, a diamino acid also detected in Mighei meteorite. Besides this intriguing question, all the remarkable properties emerged from the present investigation on ε‐lysPNAs encourage, without doubts, interest in the therapeutic and diagnostic potential of these bioinspired nucleopeptides. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.