PNA Length Restriction of Antibacterial Activity of Peptide-PNA Conjugates in Escherichia coli Through Effects of the Inner Membrane.

ABSTRACT: Peptide Nucleic Acid (PNA)-peptide conjugates targeting essential bacterial genes are showing promise as antisense antimicrobials in drug discovery. Optimization has focused on selection of target genes and exact localization around the ribosome binding site, but surprisingly a length optimum around 10-12 nucleobases has been found. Addressing this observation, we have investigated the relationship between PNA-length, PNA-RNA duplex stability and antimicrobial activity in E. coli in more detail. For PNAs of identical length of ten nucleobases the expected reverse correlation between the thermal stability (Tm) of the PNA-RNA duplex and the MIC for single mismatched PNAs was found. Also the expected direct correlation between the length of the PNA and the PNA-RNA duplex stability was

SUBMITTER: Goltermann L 

PROVIDER: S-EPMC6542938 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature