Cationic nucleopeptides as novel non-covalent carriers for the delivery of peptide nucleic acid (PNA) and RNA oligomers

Publication date: 15 May 2018
Source:Bioorganic & Medicinal Chemistry, Volume 26, Issue 9
Author(s): Stefano Tomassi, Caterina Ieranò, Maria Emilia Mercurio, Ersilia Nigro, Aurora Daniele, Rosita Russo, Angela Chambery, Ilaria Baglivo, Paolo Vincenzo Pedone, Giuseppina Rea, Maria Napolitano, Stefania Scala, Sandro Cosconati, Luciana Marinelli, Ettore Novellino, Anna Messere, Salvatore Di Maro
Cationic nucleopeptides belong to a family of synthetic oligomers composed by amino acids and nucleobases. Their capability to recognize nucleic acid targets and to cross cellular membranes provided the basis for considering them as novel non-covalent delivery agents for nucleic acid pharmaceuticals. Herein, starting from a 12-mer nucleopeptide model, the number of cationic residues was modulated in order to obtain new nucleopeptides endowed with high solubility in acqueous medium, acceptable bio-stability, low cytotoxicity and good capability to bind nucleic acid. Two candidates were selected to further investigate their potential as nucleic acid carriers, showing higher efficiency to deliver PNA in comparison with RNA. Noteworthy, this study encourages the development of nucleopeptides as new carriers to extend the known strategies for those nucleic acid analogues, especially PNA, that still remain difficult to drive into the cells.

Graphical abstract

https://ift.tt/2HLf8Mi