Tailoring peptide-nucleotide conjugates (PNCs) for nucleotide delivery in bacterial cells

The design and synthesis of peptide-2′-deoxythymidine-5′-O- monophosphate conjugates as potential active delivery systems for nucleotides into auxotrophic E. coli strains is presented. A series of oligopeptides were allowed to react with 5′-O-(dibenzylphosphate)-2′-deoxythymidine or its suitably 3′-derivatized analogues to give the relevant peptide-nucleotide adducts, by the formation of a biolabile chemical connection. Using strategies based on the principles of orthogonal protection and activation, rational variations were made to the linker and the peptide moiety in order to tune the metabolic stability of the conjugates. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.