Method of making biologically active alpha-beta peptides
AssigneeWisconsin Alumni Research Foundation
InventorsWilliam Seth Horne, Samuel H. Gellman, Lisa M. Johnson
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Abstract
Described is a method of fabricating biologically active, unnatural polypeptides. The method includes the steps of selecting a biologically active polypeptide or biologically active fragment thereof having an amino acid sequence comprising α-amino acid residues, and fabricating a synthetic polypeptide that has an amino acid sequence that corresponds to the sequence of the biologically active polypeptide, but wherein about 14% to about 50% of the α-amino acid residues found in the biologically active polypeptide or fragment of step (a) are replaced with β-amino acid residues, and the α-amino acid residues are distributed in a repeating pattern.
Claims5
A method of fabricating biologically active, unnatural polypeptides, the method comprising:
- (a) selecting a biologically active polypeptide or biologically active fragment thereof having an amino acid sequence comprising α-amino acid residues;
- and
- (b) fabricating a synthetic polypeptide that has an amino acid sequence that corresponds to the sequence of the biologically active polypeptide or fragment of step (a), wherein
- (i) in the synthetic polypeptide between about 14% and about 50% of the α-amino acid residues found in the biologically active polypeptide or fragment of step (a) are replaced with β-amino acid residues, wherein at least one of the β-amino acid residues is cyclically constrained via a ring encompassing its β2 and β3 carbon atoms, and at least one of the β-amino acid residues is unsubstituted at its β2 and β3 carbon atoms;
- (ii) in the synthetic polypeptide the β-amino acid residues and the α-amino acid residues are distributed in a repeating pattern;
- and
- (iii) the synthetic polypeptide has a length of from about 10 residues to about 100 residues and comprises at least two β-amino acid residues.
A method of fabricating a biologically active, proteoloytic-resistant, unnatural polypeptide, the method comprising:
- fabricating a synthetic polypeptide that has an amino acid sequence that corresponds to a sequence of a biologically active polypeptide or fragment thereof, wherein
- (i) in the synthetic polypeptide from about 14% to about 50% of the α-amino acid residues found in the biologically active polypeptide or fragment are replaced with analogous β-amino acid residues, wherein at least one of the β-amino acid residues is cyclically constrained via a ring encompassing its β2 and β3 carbon atoms, and at least one of the β-amino acid residues is unsubstituted at its β2 and β3 carbon atoms;
- (ii) in the synthetic polypeptide the β-amino acid residues and the α-amino acid residues are distributed in a pattern that repeats at least once.
Dependencies are inferred from the claim text.