Discovery of a novel small molecular peptide that disrupts helix 34 of bacterial ribosomal RNA

Despite the advances in modern medicine, antibiotic resistance is a persistent and growing threat to the world. Thus, the discovery and development of novel antibiotics have become crucial to combat multi-drug resistant pathogens. The goal of our research is to discover a small molecular peptide that can disrupt the synthesis of new ribosomes. Using the phage display technique, we have discovered a 7-mer peptide that binds to the second strand of 16S h34 RNA with a dissociation constant in the low micromolar range. Binding of the peptide alters RNA structure and inhibits the binding of the ribosomal RNA small subunit methyltransferase C (RsmC) enzyme that methylates the exocyclic amine of G1207. The addition of this peptide also increases the lag phase of bacterial growth. Introduction of chemical modifications to increase the binding affinity of the peptide to RNA, its uptake and stability can further improve the efficacy of the peptide as an antibiotic agent against pathogenic bacteria.