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AssigneeTechnische Universitaet Muenchen
InventorsArne Skerra, Winfried Meining, Evelyn Eggenstein
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The present disclosure relates to a collection of novel muteins derived from human α1m (or a1m) polypeptide or a functional homologue thereof. The disclosure further refers to a α1m mutein capable of specifically binding to one or more targets other than a target to which wild-type α1m binds. The disclosure also relates to a method for producing such collection of muteins and a method for isolating a mutein capable of binding one or more such non-natural targets of wild-type α1m polypeptide. These aspects are made possible due to, e.g, the structural elucidation of α1m disclosed herein by the present inventors, an appreciation of ligand-binding sights thereof and, hence, an understanding of which amino acid positions are most suitable for mutagenesis for re-engineering specificity and affinity for any given target while maintaining the secondary and/or tertiary structure of α1m.
A collection of at least 10̂2 amino acid sequence members comprised of muteins of human a1m polypeptide or a functional homologue thereof, wherein the amino acid sequence of said members differs from human a1m polypeptide at one or more of the sequence positions which correspond to the sequence positions in the four peptide loops #1, #2, #3 and #4 of human a1m polypeptide, wherein the amino acid sequence of said members differs from human a1m polypeptide at one or more of the sequence positions which correspond to the linear polypeptide sequence positions 29-48, 63-80, 89-100, and 115-129 of human a1m polypeptide and wherein the members of said collection have at least 60% sequence identity with human a1m polypeptide.
5-9. (canceled)
A mutein derived from human a1m polypeptide or a functional homologue thereof, wherein the mutein comprises at least one mutated amino acid residues at any sequence position in the four peptide loops #1, #2, #3 and #4, wherein said a1m or functional homologue thereof has at least 60% sequence homology with human mature a1m sequence, wherein the mutein comprises at least one mutated amino acid residues at any sequence position corresponding to sequence positions 29-48, 63-80, 89-100, and 115-129 of human mature a1m sequence and wherein the mutein can bind a target other than a target to which wild-type a1m binds and wherein the mutein has no or no substantial binding affinity for endogenous a1m target.
18-20. (canceled)
An a1m crystal having space group P3221 and unit-cell parameters a=b=66.72, c=80.26, a=b=90.0, g=120.0.
Dependencies are inferred from the claim text.