Peptides containing N-substituted L-amino acids for preventing β-strand association
AssigneeSenexis Limited
InventorKelvin Stott
Life of this patent
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Abstract
Peptide is disclosed which is capable of binding to β-strand in a separate peptide-containing molecule to form β-sheet, wherein said peptide is selectively Nα-substituted in one edge (first) of the β-strand-forming section of said peptide while the other edge (second) in the opposite orientation to the first edge in view of peptide backbone plane remains Nα-unsubstituted. Such the Nα-substituted peptide is capable of preventing association of said peptide with other β-strand (target) but permits interaction of said peptide with target β-strand in separate peptide-containing molecules through the Nα-unsubstituted edge.
Claims31
A peptide comprising a peptide, wherein:
- (a) said peptide comprises a β-strand-forming section, said section consisting of four to sixteen consecutive α-L-amino acid residues and encompassing at least 50% of the length of said peptide, none of the α-L-amino acid residues within the β-strand-forming section being proline, except at very ends of the β-strand-forming section;
- (b) each of the consecutive α-L-amino acid residues in the β-strand-forming section has a side chain;
- (c) said β-strand-forming section forms a β-strand having a peptide backbone which takes on the form of an extended ribbon having two edges, a first edge which associates with a target β-strand formed by a separate peptide-containing molecule and a second edge, such that the NH and CO components of successive α-L-amino acid residues lie along the first edge and the second edge of the ribbon, the first edge and second edge corresponding to two opposite edges of the plane of the ribbon, and the side chains of the consecutive α-L-amino acid residues being alternatively above or below the plane of the ribbon;
- (d) at least one of the Nα-atoms within the peptide backbone of the β-strand is Nα-substituted with an Nα-substituent, such that one or more Nα-substituent lie along only the second edge and sterically hinder the association of the second edge with another β-strand;
- and
- (e) the first edge remains free of Nα-substituents, and is not prevented from associating with the target β-strand formed by a separate peptide-containing molecule.
A peptide comprising, wherein:
- (a) said peptide comprises a β-strand-forming section consisting of four to sixteen consecutive α-L-amino acid residues and encompassing at least 50% of the length of said peptide, none of the α-L-amino acid residues within the β-strand-forming section being proline;
- (b) each of the consecutive α-L-amino acid residues in the β-strand-forming section has a side chain;
- (c) said β-strand-forming section forms a β-strand having a peptide backbone which takes on the form of an extended ribbon having two edges, a first edge which associates with a target β-strand formed by a separate peptide-containing molecule and a second edge, such that the NH and CO components of successive α-L-amino acid residues lie along the first edge and the second edge of the ribbon, the first edge and second edge corresponding to two opposite edges of the plane of the ribbon, and the side chains of the consecutive α-L-amino acid residues being alternatively above or below the plane of the ribbon;
- (d) at least one of the Nα-atoms within the peptide backbone of the β-strand is Nα-substituted with an Nα-substituent, such that one or more Nα-substituent lie along only the second edge and sterically hinder the association of the second edge with another β-strand;
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- (e) the first edge remains free of Nα-substituents, and is not prevented from associating with the target β-strand formed by a separate peptide-containing molecule.
Dependencies are inferred from the claim text.