Abstract: Provided herein are fusion polypeptides in which a small polypeptide is modified by fusion with N- and C-termini sequences that interact with one another when in proximity. In some embodiments, the small polypeptide is a cysteine motif binding peptide or a cytokine. Also provided herein are cysteine motif binding peptides, such as from the knob region of an ultralong CDR3, and methods of producing and using the same. Also provided herein are compositions comprising the binding peptides.

Abstract: The present disclosure relates to methods of producing and screening libraries of disulfide rich proteins, for instance to identify binding peptides specific for a target molecule. In some embodiments, the binding peptides comprise disulfide rich proteins. Also provided herein are methods of producing and screening libraries comprising disulfide-rich proteins and molecular chaperones. The present disclosure also relates to methods of producing or expressing soluble disulfide rich proteins, for instance using a suitable host cell. Also provided herein are compositions comprising soluble disulfide rich proteins.

Abstract: Provided are peptides able to bind a receptor that mediates receptor-mediating transcytosis (RMT) across the blood-brain barrier (BBB), as well as binding molecules that incorporate the peptides. Also provided are conjugates, including fusion proteins, composed of the peptides or binding molecules and a therapeutic or diagnostic agent. In some embodiments, the conjugates are able to pass through the blood-brain barrier after being parenterally administered to allow for function of the therapeutic or diagnostic agent in the central nervous system. Also provided are methods of making and using the provided peptides and molecules.

Abstract: Provided are chimeric antibodies containing an ultralong CDR3, such as based on a bovine antibody sequence or a humanized sequence thereof, in which a portion of the CDR3 of the heavy chain is replaced by a heterologous sequence, for instance that of interleukin (IL)-15 or IL-2, and related antibodies. Among the molecules of the present disclosure are chimeric IL-15 modified antibody molecules that are further linked or complexed with an extracellular portion of IL15R?, such as the IL15R? sushi domain. The present disclosure also provides methods of making and using the chimeric antibodies.

Abstract: Provided herein are binding polypeptides, such as binding peptides and antibodies, against a SARS CoV-2. The binding polypeptides relate to or are based on bovine antibodies, particularly those containing an ultralong CDR3. Also provided herein are methods of treating a virus infection, such as a coronavirus infection, by delivering to a subject in need a provided binding polypeptide.

Abstract: The present disclosure relates to methods of producing and screening display libraries of disulfide-bonded binding polypeptides, for instance to identify binding peptides specific for a target molecule. In some embodiments, the binding peptides comprise an ultralong CDR3. The binding peptides can be derived from a bovine antibody comprising an ultralong CDR3, or they can be synthetic or semisynthetic. Also provided herein are display libraries comprising disulfide-bonded binding polypeptides. The present disclosure also relates to methods of producing or expressing soluble disulfide-bonded binding polypeptides, for instance using a suitable host cell. Also provided herein are compositions comprising soluble disulfide-bonded binding polypeptides.

Abstract: A modified igNAR peptide sequence derived from a wild-type igNAR peptide sequence is diversified by mutating the amino acid sequence at 50% or more of the amino acids in the CDR3 loop region and optionally at 50% or more of the amino acids in the CDR3 loop region. The modified igNAR peptide may have the sequence of SEQ ID NO: 8, 10 or 50 to 85. The modified igNAR peptides have binding activity against albumin protein sequences, such as human serum albumin. These modified igNAR peptides may have utility in extending the in vivo half-life of biological molecules e.g. therapeutic agents, and so may be used in medicine.

Abstract: There is described a method of isolating nucleotide sequences encoding target peptides from DNA libraries using DNA binding proteins to link the peptide to the sequence which encodes it. DNA libraries are prepared from cells encoding the protein of interest, or from synthetic DNA, and inserted into, or adjacent to, a DNA binding protein in an expression vector to create a chimeric fusion protein. Incorporation of the vector DNA into a carrier package, during expression of the chimeric fusion protein, results in the production of a peptide display carrier package (PDCP) displaying the DNA-bound fusion protein on the external surface of the carrier package. Employment of affinity purification techniques results in the PDCP particles containing sequences encoding the desired peptide to be selected and the desired nucleotide sequences obtained therefrom.

Abstract: The invention provides a method for making in vitro peptide expression libraries, and for the isolation of nucleotide sequences encoding peptides of interest, wherein the peptides or proteins are specifically associated with the DNA encoding them through non-covalent protein:DNA binding. The method describes ways of making the library itself, DNA molecules encoding the library and uses of the expression library.

Abstract: A method is selects membrane-translocating peptides (MTPs) from a peptide display library that are capable of crossing or penetrating a lipid membrane. A plurality of nucleic acid constructs that encode displayed peptides are expressed, resulting in the formation of a plurality of nucleic acid-peptide complexes, each complex comprising at least one displayed peptide associated with the corresponding nucleic acid construct encoding the displayed peptide; the complexes are exposed to a population of membrane-encapsulated compartments, allowing a translocating reaction to occur; complexes that remain unassociated with the membrane are removed; optionally complexes that are associated with the membrane are removed; and internalized nucleic acid-peptide complexes are recovered. The membrane-encapsulated compartments may be artificial vesicles such as liposomes, or populations of one or more cell types.

Abstract: A pivot joint includes a first component (12) having a projecting boss form (16) and a second component (11) having an opening (25) for receiving the boss form (16). A headed fastener (32) and washer (27) engage with the boss form (16), which includes engagement elements (17) that dig into the washer (27) when the joint is assembled.

Abstract: The invention provides a method for making in vitro peptide expression libraries, and for the isolation of nucleotide sequences encoding peptides of interest, wherein the peptides or proteins are specifically associated with the DNA encoding them through non-covalent protein:DNA binding. The method describes ways of making the library itself, DNA molecules encoding the library and uses of the expression library.

Abstract: The invention provides a method for making in vitro peptide expression libraries, and for the isolation of nucleotide sequences encoding peptides of interest, wherein the peptides or proteins are specifically associated with the DNA encoding them through non-covalent protein:DNA binding. The method describes ways of making the library itself, DNA molecules encoding the library and uses of the expression library.

Abstract: A pivot joint includes a first component (12) having a projecting boss form (16) and a second component (11) having an opening (25) for receiving the boss form (16). A headed fastener (32) and washer (27) engage with the boss form (16), which includes engagement elements (17) that dig into the washer (27) when the joint is assembled.

Abstract: A method is provided for selecting membrane-translocating peptides (MTPs) from a peptide display library that are capable of crossing or penetrating a lipid membrane. A plurality of nucleic acid constructs that encode displayed peptides are expressed, resulting in the formation of a plurality of nucleic acid-peptide complexes, each complex comprising at least one displayed peptide associated with the corresponding nucleic acid construct encoding the displayed peptide; the complexes are exposed to a population of membrane-encapsulated compartments, allowing a translocating reaction to occur; complexes that remain unassociated with the membrane are removed; optionally complexes that are associated with the membrane are removed; and internalised nucleic acid-peptide complexes are recovered. The membrane-encapsulated compartments may be artificial vesicles such as liposomes, or populations of one or more cell types.

Abstract: There is described a method of isolating nucleotide sequences encoding target peptides from DNA libraries using DNA binding proteins to link the peptide to the sequence which encodes it. DNA libraries are prepared from cells encoding the protein of interest, or from synthetic DNA, and inserted into, or adjacent to, a DNA binding protein in an expression vector to create a chimeric fusion protein. Incorporation of the vector DNA into a carrier package, during expression of the chimeric fusion protein, results in the production of a peptide display carrier package (PDCP) displaying the DNA-bound fusion protein on the external surface of the carrier package. Employment of affinity purification techniques results in the PDCP particles containing sequences encoding the desired peptide to be selected and the desired nucleotide sequences obtained therefrom.

Abstract: There is described a method of isolating nucleotide sequences encoding target peptides from DNA libraries using DNA binding proteins to link the peptide to the sequence which encodes it. DNA libraries are prepared from cells encoding the protein of interest, or from synthetic DNA, and inserted into, or adjacent to, a DNA binding protein in an expression vector to create a chimeric fusion protein. Incorporation of the vector DNA into a carrier package, during expression of the chimeric fusion protein, results in the production of a peptide display carrier package (PDCP) displaying the DNA-bound fusion protein on the external surface of the carrier package. Employment of affinity purification techniques results in the PDCP particles containing sequences encoding the desired peptide to be selected and the desired nucleotide sequences obtained therefrom.

Abstract: The invention provides a method for making in vitro peptide expression libraries, and for the isolation of nucleotide sequences encoding peptides of interest, wherein the peptides or proteins are specifically associated with the DNA encoding them through non-covalent protein:DNA binding. The method describes ways of making the library itself, DNA molecules encoding the library and uses of the expression library.