摘要:
The present invention provides influenza hemagglutinin stem domain polypeptides comprising (a) an influenza hemagglutinin HA1 domain that comprises an HA1 N- terminal stem segment, covalently linked by a linking sequence of 0-50 amino acid residues to an HA1 C- terminal stem segment, and (b) an influenza hemagglutinin HA2 domain, wherein on or more amino acids in the HA2 domain have been mutated. Also provided are nucleic acids encoding the polypeptides, compositions comprising the polypeptides and/or nucleic acid molecules, as well as methods of their use, in particular in the detection, prevention and/or treatment of influenza.
摘要:
A method of designing a D-polypeptide that binds with an L-target protein can include: identifying a polypeptide target having L-chirality; determining hotspot amino acids of a polypeptide ligand having L-chirality that have binding interactions with the L-target protein; determining transformations of side chains of the hotspot amino acids that retain the binding interactions with the target; generating inversed hotspot amino acids with chirality opposite to the one of the target; identifying a polypeptide having inverse chirality from the target protein, on which a combination of inversed hotspot amino-acid can be grafted without significantly changing their interactions with the target. The designed ligands can be processed and converted to D-ligands that bind with the L-target protein.
摘要:
Monomeric and multimeric binding molecules that are capable of specifically binding to hemagglutinin (HA) of at least two influenza A virus strains, said strains including HA of two different HA subtypes from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically binding to hemagglutinin (HA) of at least one influenza B virus strain are provided. The binding molecules preferably are also capable of neutralizing at least two influenza A virus strains from phylogenetic group 2; or capable of neutralizing at least one influenza A virus strain from phylogenetic group 1 and at least one influenza A virus strain from phylogenetic group 2; or capable of specifically neutralizing at least one influenza B virus strain.