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

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-epsilon-peptide that we called epsilon-lysPNA. The ability to bind complementary RNA and the stability in serum of this synthetic nucleo-epsilon-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 epsilon-peptides and other epsilon-amino acid-containing compounds in natural products with biological activity such as the poly-epsilon-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 epsilon-peptides, and not alpha-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 epsilon-lysPNAs encourage, without doubts, interest in the therapeutic and diagnostic potential of these bioinspired nucleopeptides.