Abstract: The present disclosure provides methods of treating COVID-19 by administering a pharmaceutical composition providing inhibition of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (MPro) in a patient. The disclosure also provides other methods as well as pharmaceutical formulations for use in treating COVID-19 patients.

Abstract: The present disclosure relates to certain molecules, pharmaceutical compositions containing them, and methods of using them to treat viral infections.

Abstract: Embodiments of the present disclosure pertain to methods of selecting cyclic peptides that bind to a target by transforming a phage display library with a plurality of nucleic acids into bacterial host cells, where the nucleic acids include phage coat protein genes with a combinatorial region that encodes at least one cysteine and at least one non-canonical amino acid. The transformation results in the production of phage particles with phage coat proteins where the cysteine and the non-canonical amino acid couple to one another to form a cyclic peptide library. Phage particles are then screened against the desired target to select bound cyclic peptides. Amino acid sequences of the selected cyclic peptides are then identified. Additional embodiments pertain to methods of constructing a phage display library that encodes the cyclic peptides. Further embodiments of the present disclosure pertain to the produced cyclic peptides, phage display libraries and phage particles.

Abstract: Embodiments of the present disclosure pertain to methods of conjugating a molecule to a polypeptide by (1) modifying one or more thiol residues on the polypeptide, where the modifying includes cyanylation of the one or more thiol residues; and (2) associating the polypeptide with the molecule, where the associating results in the conjugation of the molecule to the polypeptide through a reaction between a nucleophilic moiety on the molecule and the one or more modified thiol residues. The cyanylation may include attachment of cyano groups to sulfur atoms of the one or more thiol residues to form thiocyanato groups that undergo reversible intramolecular addition with a nearby N-amide group to generate a 1-acyl-2-iminothiazolidine intermediate. Thereafter, the nucleophilic moiety on the molecule reacts with the 1-acyl-2-iminothiazolidine intermediate to replace 2-iminothiazolidine in a nucleophilic acyl substitution reaction and result in the conjugation of the molecule to the polypeptide.

Abstract: The present disclosure provides methods of treating COVID-19 by administering a pharmaceutical composition providing inhibition of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (MPro) in a patient. The disclosure also provides other methods as well as pharmaceutical formulations for use in treating COVID-19 patients.

Abstract: The present disclosure relates to certain molecules, pharmaceutical compositions containing them, and methods of using them to treat viral infections.

Abstract: Embodiments of the present disclosure pertain to methods of constructing a phage display library where at least 90% of combinatorial regions in the phage display library include at least one in-frame amber codon. Further embodiments of the present disclosure pertain to the formed phage display libraries. Additional embodiments of the present disclosure pertain to methods of selecting peptides or proteins that bind to a desired target (e.g., a ligand binding site of a desired target) by utilizing the phage display libraries of the present disclosure. Further embodiments of the present disclosure pertain to peptides that have been screened from the phage display libraries and methods of the present disclosure, such as inhibitors of sirtuin 2, or inhibitors of ENL.

Abstract: The present disclosure pertains to methods of producing recombinant peptides that contain between 10 and 200 amino acid residues using novel carrier proteins derived from superfolder green fluorescent protein and its mutants.

Abstract: The present disclosure pertains to methods of producing recombinant peptides that contain between 10 and 200 amino acid residues using novel carrier proteins derived from superfolder green fluorescent protein and its mutants.

Abstract: The present disclosure pertains to methods of producing recombinant peptides that contain between 10 and 200 amino acid residues using novel carrier proteins derived from superfolder green fluorescent protein and its mutants.

Abstract: The present disclosure pertains to methods of producing recombinant peptides that contain between 10 and 200 amino acid residues using novel carrier proteins derived from superfolder green fluorescent protein and its mutants.

Abstract: The present disclosure pertains to methods of producing recombinant peptides that contain between 10 and 200 amino acid residues using novel carrier proteins derived from superfolder green fluorescent protein and its mutants.

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate unnatural amino acids into proteins in mammalian host cells, for example, primate host cells and rodent host cells. The invention provides, for example but not limited to, translation systems that include host cells (e.g., primate or rodent cells), orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNAs, and the unnatural amino acid. The invention also relates to methods for producing proteins of interest comprising at least one unnatural amino acid in mammalian host cell systems.

Abstract: The present disclosure pertains to methods of producing recombinant peptides that contain between 10 and 200 amino acid residues using novel carrier proteins derived from superfolder green fluorescent protein and its mutants.

Abstract: The present disclosure pertains to methods of incorporating one or more non-canonical amino acids into a protein during a translation of the protein in bacterial cells. The present disclosure also pertains to methods of incorporating one or more non-canonical amino acids into a protein during an in vitro translation of the protein. In additional embodiments, the present disclosure pertains to isolated bacterial cells and in vitro translation systems (e.g., cell-free extract systems) for incorporating one or more non-canonical amino acids into a protein during a translation of the protein.

Abstract: The invention relates to methods, systems, and compositions for the genetic incorporation of a plurality of different noncanonical amino acids into one target protein. The invention provides for multiple, mutually orthogonal aminoacyl-tRNA synthetase/tRNA pairs that suppress two different selector codons engineered into a polynucleotide molecule. By virtue of the suppression of the selector codons, orthogonal aminoacyl-tRNA synthetase/tRNA pairs permit incorporation of their charged noncanonical amino acids into the corresponding positions in the protein. The noncanonical amino acids provide a wide array of functional capabilities. For example, the noncanonical amino acids can provide a reactive pair of moieties that facilitate the study and manipulation of the target protein.

Abstract: The present disclosure pertains to methods of incorporating one or more non-canonical amino acids into a protein during a translation of the protein in bacterial cells. The present disclosure also pertains to methods of incorporating one or more non-canonical amino acids into a protein during an in vitro translation of the protein. In additional embodiments, the present disclosure pertains to isolated bacterial cells and in vitro translation systems (e.g., cell-free extract systems) for incorporating one or more non-canonical amino acids into a protein during a translation of the protein.

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate unnatural amino acids into proteins in mammalian host cells, for example, primate host cells and rodent host cells. The invention provides, for example but not limited to, translation systems that include host cells (e.g., primate or rodent cells), orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNAs, and the unnatural amino acid. The invention also relates to methods for producing proteins of interest comprising at least one unnatural amino acid in mammalian host cell systems.

Abstract: The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate unnatural amino acids into proteins in mammalian host cells, for example, primate host cells and rodent host cells. The invention provides, for example but not limited to, translation systems that include host cells (e.g., primate or rodent cells), orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNAs, and the unnatural amino acid. The invention also relates to methods for producing proteins of interest comprising at least one unnatural amino acid in mammalian host cell systems.