Abstract: Disclosed are engineered polynucleotides, engineered ribosomes comprising the engineered polynucleotides, engineered cells and systems comprising the engineered polynucleotides and ribosomes, and methods of making and using the engineered polynucleotides, engineered ribosomes, engineered cells and systems. The engineered polynucleotides, engineered ribosomes, and engineered cells may be utilized to prepare sequence defined polymers and to select for mutant ribosomes that are capable of incorporating non-canonical amino acids into a polymer.

Abstract: An engineered ribosome that includes a tethered subunit arrangement is disclosed, in which the engineered ribosome supports translation of a sequence defined polymer. Methods for making and using the engineered ribosome are also disclosed, including a method for preparing a sequence defined polymer using the engineered ribosome and a method for preparing a sequence defined polymer using the engineered ribosome in a two-protein translation system. The engineered ribosomes may be utilized in methods for incorporating unnatural amino acids into a sequence defined polymer. Also disclosed are optimized polynucleotide sequences for use as tethers and Shine-Dalgarno/anti-Shine-Dalgarno sequences.

Abstract: An engineered ribosome that includes a tethered subunit arrangement is disclosed, in which the engineered ribosome supports translation of a sequence defined polymer. Methods for making and using the engineered ribosome are also disclosed, including a method for preparing a sequence defined polymer using the engineered ribosome and a method for preparing a sequence defined polymer using the engineered ribosome in a two-protein translation system. The engineered ribosomes may be utilized in methods for incorporating unnatural amino acids into a sequence defined polymer. Also disclosed are optimized polynucleotide sequences for use as tethers and Shine-Dalgarno/anti-Shine-Dalgarno sequences.

Abstract: The present invention discloses compositions of peptide inhibitors of protein synthesis, and methods of identifying peptide inhibitors that are capable of inhibiting protein synthesis through an interaction at a stem-loop H18 in 16S rRNA of a 30S ribosomal subunit. Screening methods for peptides are disclosed, in addition to methods of determining the affinity of a test compound for a ribosomal subunit.

Abstract: The present invention discloses compositions of peptide inhibitors of protein synthesis, and methods of identifying peptide inhibitors that are capable of inhibiting protein synthesis through an interaction at a stem-loop H18 in 16S rRNA of a 30S ribosomal subunit. Screening methods for peptides are disclosed, in addition to methods of determining the affinity of a test compound for a ribosomal subunit.

Abstract: Improved antibiotic analogs, and synergistic combinations of antibiotics designed based on structural crystallographic analysis, are provided as well as pharmaceutical compositions that include these improved analogs and synergistic combinations, along with methods for their production and use. The synergistic combinations target neighboring sites in the ribosome demonstrating the importance of the corresponding ribosomal sites for development of clinically-relevant synergistic antibiotics.

Abstract: The present invention discloses compositions of peptide inhibitors of protein synthesis, and methods of identifying peptide inhibitors that are capable of inhibiting protein synthesis through an interaction at a stem-loop H18 in 16S rRNA of a 30S ribosomal subunit. Screening methods for peptides are disclosed, in addition to methods of determining the affinity of a test compound for a ribosomal subunit.