Does a Conjugation Site Affect Transport of Vitamin B12 -Peptide Nucleic Acid Conjugates into Bacterial Cells?

Chemistry. 2018 Dec 12;24(70):18772-18778. doi: 10.1002/chem.201804304. Epub 2018 Nov 15.


Gram-negative bacteria develop specific systems for the uptake of scarce nutrients, including vitamin B12 . These uptake pathways may be utilized for the delivery of biologically relevant molecules into cells. Indeed, it was recently reported that vitamin B12 transported an antisense peptide nucleic acid (PNA) into Escherichia coli and Salmonella Typhimurium cells. The present studies indicate that the conjugation site of PNA to vitamin B12 has an impact on PNA transport into bacterial cells. Toward this end, a specifically designed PNA oligomer has been tethered at various positions of vitamin B12 (central Co, R5' -OH, c and e amide chains, meso position, and at the hydroxy group of cobinamide) by using known or newly developed methodologies and tested for the uptake of the synthesized conjugates by E. coli. Compounds in which the PNA oligonucleotide was anchored at the R5' -OH position were transported more efficiently than that of other compounds tethered at the peripheral positions around the corrin ring. Of importance is the fact that, contrary to mammalian organisms, E. coli also takes up cobinamide, which is an incomplete corrinoid. This selectivity opens up ways to fight bacterial infections.

Keywords: bioconjugation; drug delivery; natural products; peptide nucleic acids; structure-activity relationships.

MeSH terms

  • Alkynes / chemistry
  • Azides / chemistry
  • Biological Transport
  • Catalysis
  • Copper / chemistry
  • Cycloaddition Reaction
  • Drug Carriers / chemistry
  • Escherichia coli / metabolism*
  • Peptide Nucleic Acids / chemistry*
  • Salmonella typhimurium / metabolism*
  • Vitamin B 12 / chemistry*
  • Vitamin B 12 / metabolism


  • Alkynes
  • Azides
  • Drug Carriers
  • Peptide Nucleic Acids
  • Copper
  • Vitamin B 12