Stabilized bioactive peptides and methods of identification, synthesis, and use
AssigneeUniversity of Georgia Research Foundation, Inc.
InventorElliot ALTMAN
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Abstract
An intracellular selection system allows screening for peptide bioactivity and stability. Randomized recombinant peptides are screened for bioactivity in a tightly regulated expression system, preferably derived from the wild-type lac operon. Bioactive peptides thus identified are inherently protease- and peptidase-resistant. Also provided are bioactive peptides stabilized by a stabilizing group at the N-terminus, the C-terminus, or both. The stabilizing group can be a small stable protein, such as the Rop protein, glutathione sulfotransferase, thioredoxin, maltose binding protein, or glutathione reductase, an α-helical moiety, or one or more proline residues.
Claims29
A polypeptide comprising a bioactive peptide and a first stabilizing group coupled to a terminus of said bioactive peptide, wherein said first stabilizing group is heterologous to the bioactive peptide and lacks the capacity to participate in the formation of an intramolecular disulfide bond within the polypeptide.
A polypeptide comprising a bioactive peptide and a stabilizing group coupled to a terminus of said bioactive peptide, wherein said stabilizing group is not a thioredoxin polypeptide.
A polypeptide comprising a bioactive peptide, a first stabilizing group coupled to the N-terminus of said bioactive peptide and a second stabilizing group coupled to the C-terminus of said bioactive peptide, wherein said first and second stabilizing groups are heterologous to the bioactive peptide and to each other.
A polypeptide comprising a bioactive peptide, a first stabilizing group coupled to the N-terminus of said bioactive peptide and a second stabilizing group coupled to the C-terminus of said bioactive peptide, wherein said first and second stabilizing groups are heterologous to the bioactive peptide and do not interact to form a naturally occurring secondary or tertiary structure.
A polypeptide comprising a bioactive peptide, a first stabilizing group coupled to the N-terminus of said bioactive peptide and a second stabilizing group coupled to the C-terminus of said bioactive peptide, wherein said first stabilizing group and second groups are heterologous to the bioactive peptide and do not confine the N-terminus and the C-terminus of the bioactive peptide in close proximity.
A polypeptide comprising a bioactive peptide and a first stabilizing group coupled to a terminus of said bioactive peptide, said bioactive peptide having been identified using a phage display process that produces a bacteriophage protein coupled to one terminus of said bioactive peptide, wherein the stabilizing group takes the place of the bacteriophage protein.
A polypeptide comprising a bioactive peptide and a first stabilizing group coupled to one terminus of said bioactive peptide, and a second stabilizing group coupled to the other terminus of said bioactive peptide, wherein said bioactive peptide is 50 or fewer amino acids in length, and wherein said first stabilizing group is human serum albumin or a fragment thereof.
Dependencies are inferred from the claim text.