Abstract: A method is disclosed for identifying a member of a peptide library that interacts with a target molecule in situ, the method including expressing immobilised nucleic acid molecules to produce the peptide library in a way that each member of the peptide library is immobilised on the nucleic acid molecule from which it was expressed; contacting the immobilised peptide library with the target molecule; and detecting an interaction between at least one member of the peptide library and the target molecule. The method further comprises sequencing the plurality of nucleic acid molecules in situ on the solid support, such that the at least one member of the peptide library that interacts with the target molecule can be immediately identified, at least by the sequence of the nucleic acid molecule from which it was expressed, without requiring additional or secondary analysis or characterising procedures in order to identify the useful members of the library.

Abstract: A naive WW domain peptide library derived from a WW domain peptide sequence which has been diversified by changing the amino acid sequence at one or more positions is provided. The naive WW domain peptide library may be derived from a GroupIV WW domain peptide. Methods for making the naive WW domain peptide library and methods for selected a modified WW domain peptide that binds a target ligand using the naive WW domain peptide library are also provided. Also disclosed are modified WW domain peptides that bind desired target ligands, pharmaceutical compositions comprising such peptides, and uses for such peptides. The modified WW domain peptides have altered, improved or different, target ligand binding characteristics to those of the unmodified WW domain peptides from which they are derived.

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 method is provided for isolating protease resistant antimicrobial peptides (AMPs) from a peptide display library. A plurality of nucleic acid constructs that encode displayed peptides are expressed, resulting in the formation of a plurality of peptide-nucleic acid 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 at least one protease, to allow the proteolysis of protease-sensitive peptides, such that resistant peptides remain. The peptide-nucleic acid complexes are further exposed to a membrane composition to allow association of complexes that contain membrane-associating peptides. Complexes that remain unassociated with the membrane are removed; and membrane-associated complexes are recovered. The AMPs so characterised may be resistant to one or more protease enzymes and exhibit antimicrobial activity against one or more microbe.

Abstract: Peptide stabilizer compounds are provided that in combination with a biologically active peptide, can increase the protease elimination half-time of the biologically active peptide in vivo. The peptide stabilizer compounds are preferably in the form of peptide sequences that confer resistance to proteolysis upon conjugated biologically active peptides. Also provided is a method for the selection of novel proteolysis resistant compounds from in vitro generated libraries, and pharmaceutical compositions comprising the stabilizer compounds identified thereby.

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.