Short peptides which selectively modulate the activity of protein kinases
AssigneesChildren's Medical Center Corporation, Yissum Research Development Company
InventorShmuel A. Ben-Sasson
Life of this patent
Estimating the term…
Abstract
Peptides which are peptide derivatives of the αD region of a protein kinase can modulate the activity of protein kinases. The activity of a protein kinase in a subject can be modulated by administering one or more of these peptides.
Claims34
A peptide capable of modulating the activity of a protein kinase having a structure that includes the twelve subdomains and nine alpha helices that are characteristic of the protein kinase superfamily, consisting of:
- a) an αD region peptide consisting of a sequence of about 20 amino acid residues of the protein kinase Subdomain V and the beginning of Subdomain VI, beginning at the end of the b5 beta sheet and extending through the D helix and the following loop to the beginning of helix E, which amino acids correspond to a continuous stretch of the prototypical PKA-Cα in positions 120-139 of the PKA-Cα, and which αD region peptide modulates the activity of the protein kinase;
- b) a subsequence peptide consisting of a subsequence of a) consisting of at least five contiguous amino acids thereof, which subsequence peptide modulates the activity of the protein kinase;
- c) a modified sequence peptide having a modified sequence of a) or b) in which up to two residues are each substituted by another amino acid residue or amino acid residue analog other than one which is identical to the one being substituted except that a functional group in the side chain is functionalized with a protecting group, which modified sequence peptide modulates the activity of the protein kinase;
- d) a protected peptide a), b) or c) in which the N-terminus and/or the C-terminus is protected by a protecting group and/or one or more side chains of the amino acid residues of the peptide of a), b) or c) have been functionalized with a protecting group, which protected peptide modulates the activity of the protein kinase;
- or
- e) a cyclized peptide of a), b), c) or d) which has been cyclized, which cyclized peptide modulates the activity of the protein kinase, wherein the peptide has the sequence of SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114 SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, or SEQ ID NO:170.
A peptide having the sequence of SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:127, SEQ ED NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:150, SEQ ID NO:151, SEQ ID NO:152, SEQ ID NO:153, SEQ ID NO:154, SEQ ID NO:155, SEQ ID NO:156, SEQ ID NO:157, SEQ ID NO:158, SEQ ID NO:159, SEQ ID NO:160, SEQ ID NO:161, SEQ ID NO:162, SEQ ID NO:163, SEQ ID NO:164, SEQ ID NO:165, SEQ ID NO:166, SEQ ID NO:167, SEQ ID NO:168, SEQ ID NO:169, or SEQ ID NO:170, with the proviso that any one amino acid residue in the peptide can be substituted by another amino acid residue or amino acid residue analog.
A peptide consisting of a sequence of amino acids AA1 through AA23 or a subsequence thereof comprising at least five amino acids, wherein:
- AA1 is selected from the group consisting of leucine, methionine, isoleucine and valine;
- AA2 is selected from the group consisting of aspartic acid, threonine, glutamic acid, serine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of a glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA4 is selected from the group consisting of methionine, isoleucine, leucine and valine;
- AA5 is selected from the group consisting of asparagine and glutamine;
- AA6 is selected from the group consisting of glycine and alanine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of a glutamic acid or aspartic acid;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of histidine, arginine and lysine;
- AA11 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA12 is histidine;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of serine, tyrosine, threonine, phenylalanine and tryptophan;
- AA15 is selected from the group consisting of glutamine, asparagine and histidine;
- AA16 is selected from the group consisting of histidine, valine, leucine, methionine and isoleucine;
- AA17 is selected from the group consisting of glycine, aspartic acid, glutamic acid, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of a glutamic acid or aspartic acid;
- AA18 is selected from the group consisting of valine, glutamic acid, asparagine, glutamine, isoleucine, leucine, methionine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of a glutamic acid or aspartic acid;
- AA19 is selected from the group consisting of phenylalanine, aspartic acid, proline, alanine, tryptophan, tyrosine, glutamic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of a glutamic acid or aspartic acid;
- AA20 is selected from the group consisting of asparagine, glycine, glutamine and alanine;
- AA21 is selected from the group consisting of proline, phenylalanine, tryptophan and tyrosine;
- AA22 is selected from the group consisting of glycine and alanine;
- and
- AA23 is selected from the group consisting of phenylalanine, tryptophan and tyrosine, wherein the sequence AA1 through AA23 or a subsequence thereof corresponds to the sequence or a subsequence of the αD region of a G protein-coupled receptor kinase selected from the group consisting of SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21 and SEQ ID NO:22, with the proviso that any one amino acid in the sequence AA1 through AA23 or the subsequence thereof can vary as set forth above.
A peptide consisting of a sequence of amino acids AA1 through AA20 or a subsequence thereof comprising at least seven amino acids, wherein:
- AA1 is selected from the group consisting of phenylalanine, tryptophan and tyrosine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of phenylalanine, histidine, tryptophan and tyrosine;
- AA4 is selected from the group consisting of leucine, valine, isoleucine and methionine;
- AA5 is selected from the group consisting of histidine, aspartic acid, glutamic acid, and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA6 is selected from the group consisting of glutamine and asparagine;
- AA7 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA8 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA9 is selected from the group consisting of lysine, arginine, threonine and serine;
- AA10 is selected from the group consisting of lysine, threonine, arginine and serine;
- AA11 is selected from the group consisting of phenylalanine, tyrosine and tryptophan;
- AA12 is selected from the group consisting of methionine, leucine, isoleucine and valine;
- AA13 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA14 is selected from the group consisting of alanine, lysine, arginine and glycine;
- AA15 is selected from the group consisting of valine, serine, alanine, isoleucine, leucine, methionine and threonine;
- AA16 is selected from the group consisting of alanine, proline and glycine;
- AA17 is selected from the group consisting of leucine, proline, glutamic acid, isoleucine, methionine, valine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA18 is selected from the group consisting of threonine, proline and serine;
- AA19 is selected from the group consisting of glycine and alanine;
- and
- AA20 is selected from the group consisting of isoleucine, leucine, valine and methionine.
A peptide consisting of a sequence of amino acids AA1 through AA21 or a subsequence thereof comprising at least seven amino acids, wherein:
- AA1 is selected from the group consisting of threonine, methionine, serine, isoleucine, leucine and valine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of phenylalanine, tyrosine, histidine and tryptophan;
- AA4 is selected from the group consisting of methionine, valine, isoleucine and leucine;
- AA5 is selected from the group consisting of serine, asparagine, cysteine, alanine, glutamic acid, threonine, glutamine, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA6 is selected from the group consisting of lysine, histidine, asparagine, arginine and glutamine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of serine, asparagine, threonine and glutamine;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of leucine, valine, isoleucine and methionine;
- AA11 is selected from the group consisting of aspartic acid, asparagine, glutamic acid, glutamine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA12 is selected from the group consisting of phenylalanine, tyrosine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of lysine and arginine;
- AA15 is selected from the group consisting of glycine, glutamic acid, aspartic acid, asparagine, serine, threonine, glutamine, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA16 is selected from the group consisting of glutamic acid, glycine, proline, aspartic acid, arginine, lysine, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA17 is selected from the group consisting of threonine, serine, aspartic acid, glutamic acid, glycine, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA18 is selected from the group consisting of glycine, arginine, lysine and alanine;
- AA19 is selected from the group consisting of lysine, arginine, glutamine, glycine, serine, isoleucine, alanine, asparagine, threonine, leucine, methionine and valine;
- AA20 is selected from the group consisting of tyrosine, alanine, aspartic acid, lysine, valine, leucine, phenylalanine, tryptophan, glutamic acid, arginine, isoleucine, methionine, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- and
- AA21 is selected from the group consisting of leucine, valine, glutamine, isoleucine, methionine and asparagine.
A peptide consisting of a sequence of amino acids AA1 through AA39 or a subsequence thereof comprising at least seven amino acids, wherein:
- AA1 is selected from the group consisting of isoleucine, threonine, valine, leucine, methionine and serine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA4 is selected from the group consisting of alanine, cysteine, serine, thronine and glycine;
- AA5 is selected from the group consisting of glycine, arginine, phenylalanine, lysine, tryptophan and tyrosine;
- AA6 is selected from the group consisting of tyrosine, histidine, phenylalanine and tryptophan;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of asparagine, aspartic acid, glutamine, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of leucine, valine, serine, isoleucine, methionine and threonine;
- AA11 is selected from the group consisting of aspartic acid, asparagine, threonine, glutamic acid, glutamine, serine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA12 is selected from the group consisting of phenylalanine, tyrosine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of arginine, histidine and lysine;
- AA15 is selected from the group consisting of lysine, arginine, serine, alanine, glycine and threonine;
- AA16 is selected from the group consisting of serine, asparagine, lysine, threonine, glutamine and arginine;
- AA17 is selected from the group consisting of arginine and lysine;
- AA18 is selected from the group consisting of valine, histidine, aspartic acid, asparagine, isoleucine, leucine, methionine, glutamic acid, glutamine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA19 is selected from the group consisting of leucine, threonine, serine, alanine, glutamic acid, isoleucine, methionine, valine, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA20 is selected from the group consisting of glutamic acid, phenylalanine, aspartic acid, tryptophan, tyrosine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA21 is selected from the group consisting of threonine, leucine, phenylalanine, serine, valine, isoleucine, methionine, tryptophan and tyrosine;
- AA22 is selected from the group consisting of aspartic acid, glutamine, serine, leucine, proline, glutamic acid, asparagine, threonine, isoleucine, methionine, valine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA23 is selected from the group consisting of proline, histidine, asparagine, cysteine, tyrosine, glutamine, phenylalanine, tryptophan, and serine;
- AA24 is selected from the group consisting of alanine, histidine, lysine, arginine and glycine;
- AA25 is selected from the group consisting of phenylalanine, serine, proline, aspartic acid, glutamic acid, tryptophan, tyrosine, threonine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA26 is selected from the group consisting of alanine, aspartic acid, glutamic acid, lysine, arginine, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA27 is selected from the group consisting of arginine, isoleucine, lysine, alanine, serine, glycine, leucine, methionine, valine and threonine;
- AA28 is selected from the group consisting of glutamic acid, alanine, arginine, proline, leucine, aspartic acid, lysine, isoleucine, methionine, valine, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA29 is selected from the group consisting of histidine, asparagine, arginine, lysine, glutamic acid, glutamine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA30 is selected from the group consisting of glycine, serine, proline, lysine, methionine, glutamine, phenylalanine, threonine, arginine, isoleucine, leucine, valine, asparagine, tryptophan, tyrosine and alanine;
- AA31 is selected from the group consisting of threonine, proline, glutamic acid, arginine, serine, aspartic acid, lysine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA32 is selected from the group consisting of serine, alanine, aspartic acid, lysine, arginine, glycine, threonine, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA33 is selected from the group consisting of threonine, glutamic acid, isoleucine, lysine, phenylalanine, serine, aspartic acid, leucine, methionine, valine, arginine, tryptophan, tyrosine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA34 is selected from the group consisting of leucine, phenylalanine, glutamic acid, arginine, aspartic acid, isoleucine, methionine, valine, tryptophan, tyrosine, lysine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA35 is selected from the group consisting of tyrosine, glycine, lysine, alanine, phenylalanine, tryptophan and arginine;
- AA36 is selected from the group consisting of serine, leucine, methionine, valine, threonine, and isoleucine;
- AA37 is selected from the group consisting of asparagine, glutamic acid, valine, glycine, glutamine, aspartic acid, isoleucine, leucine, methionine, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA38 is selected from the group consisting of alanine, proline, glutamic acid, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA39 is selected from the group consisting of leucine, alanine, glycine, isoleucine, methionine and valine, wherein the sequence AA1 through AA39 or a subsequence thereof corresponds to the sequence of the αD region of an endothelial growth factor receptor kinase selected from the group consisting of SEQ ID NO:49 and SEQ ID NO:50 or a subsequence thereof, with the proviso that any two amino acids in the sequence AA1 through AA39 or the subsequence thereof can vary as set forth above.
A peptide consisting of a sequence of amino acids AA1 through AA39 or a subsequence thereof comprising at least seven amino acids, wherein:
- AA1 is selected from the group consisting of isoleucine, threonine, valine, leucine, methionine and serine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA4 is selected from the group consisting of alanine, cysteine, serine, thronine and glycine;
- AA5 is selected from the group consisting of glycine, arginine, phenylalanine, lysine, tryptophan and tyrosine;
- AA6 is selected from the group consisting of tyrosine, histidine, phenylalanine and tryptophan;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of asparagine, aspartic acid, glutamine, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of leucine, valine, serine, isoleucine, methionine and threonine;
- AA11 is selected from the group consisting of aspartic acid, asparagine, threonine, glutamic acid, glutamine, serine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA12 is selected from the group consisting of phenylalanine, tyrosine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of arginine, histidine and lysine;
- AA15 is selected from the group consisting of lysine, arginine, serine, alanine, glycine and threonine;
- AA16 is selected from the group consisting of serine, asparagine, lysine, threonine, glutamine and arginine;
- AA17 is selected from the group consisting of arginine and lysine;
- AA18 is selected from the group consisting of valine, histidine, aspartic acid, asparagine, isoleucine, leucine, methionine, glutamic acid, glutamine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA19 is selected from the group consisting of leucine, threonine, serine, alanine, glutamic acid, isoleucine, methionine, valine, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA20 is selected from the group consisting of glutamic acid, phenylalanine, aspartic acid, tryptophan, tyrosine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA21 is selected from the group consisting of threonine, leucine, phenylalanine, serine, valine, isoleucine, methionine, tryptophan and tyrosine;
- AA22 is selected from the group consisting of aspartic acid, glutamine, serine, leucine, proline, glutamic acid, asparagine, threonine, isoleucine, methionine, valine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA23 is selected from the group consisting of proline, histidine, asparagine, cysteine, tyrosine, glutamine, phenylalanine, tryptophan, and serine;
- AA24 is selected from the group consisting of alanine, histidine, lysine, arginine and glycine;
- AA25 is selected from the group consisting of phenylalanine, serine, proline, aspartic acid, glutamic acid, tryptophan, tyrosine, threonine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA26 is selected from the group consisting of alanine, aspartic acid, glutamic acid, lysine, arginine, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA27 is selected from the group consisting of arginine, isoleucine, lysine, alanine, serine, glycine, leucine, methionine, valine and threonine;
- AA28 is selected from the group consisting of glutamic acid, alanine, arginine, proline, leucine, aspartic acid, lysine, isoleucine, methionine, valine, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA29 is selected from the group consisting of histidine, asparagine, arginine, lysine, glutamic acid, glutamine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA30 is selected from the group consisting of glycine, serine, proline, lysine, methionine, glutamine, phenylalanine, threonine, arginine, isoleucine, leucine, valine, asparagine, tryptophan, tyrosine and alanine;
- AA31 is selected from the group consisting of threonine, proline, glutamic acid, arginine, serine, aspartic acid, lysine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA32 is selected from the group consisting of serine, alanine, aspartic acid, lysine, arginine, glycine, threonine, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA33 is selected from the group consisting of threonine, glutamic acid, isoleucine, lysine, phenylalanine, serine, aspartic acid, leucine, methionine, valine, arginine, tryptophan, tyrosine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA34 is selected from the group consisting of leucine, phenylalanine, glutamic acid, arginine, aspartic acid, isoleucine, methionine, valine, tryptophan, tyrosine, lysine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA35 is selected from the group consisting of tyrosine, glycine, lysine, alanine, phenylalanine, tryptophan and arginine;
- AA36 is selected from the group consisting of serine, leucine, methionine, valine, threonine, and isoleucine;
- AA37 is selected from the group consisting of asparagine, glutamic acid, valine, glycine, glutamine, aspartic acid, isoleucine, leucine, methionine, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA38 is selected from the group consisting of alanine, proline, glutamic acid, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA39 is selected from the group consisting of leucine, alanine, glycine, isoleucine, methionine and valine, wherein the sequence AA1 through AA39 or a subsequence thereof corresponds to the sequence of the αD region of an endothelial growth factor receptor kinase selected from the group consisting of SEQ ID NO:49 and SEQ ID NO:50 or a subsequence thereof, with the proviso that any one amino acid in the sequence AA1 through AA39 or the subsequence thereof can vary as set forth above.
A peptide consisting of a sequence of amino acids AA1 through AA34 or a subsequence thereof comprising at least seven amino acids, wherein:
- AA1 is selected from the group consisting of valine, isoleucine, leucine and methionine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of tyrosine, cysteine, phenylalanine, tryptophan and serine;
- AA4 is selected from the group consisting of alanine and glycine;
- AA5 is selected from the group consisting of serine, alanine, threonine and glycine;
- AA6 is selected from the group consisting of lysine and arginine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of asparagine and glutamine;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of arginine and lysine;
- AA11 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA12 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of glutamine, arginine, asparagine and lysine;
- AA15 is selected from the group consisting of alanine and glycine;
- AA16 is selected from the group consisting of arginine and lysine;
- AA17 is selected from the group consisting of arginine and lysine;
- AA18 is proline;
- AA19 is proline;
- AA20 is selected from the group consisting of glycine and alanine;
- AA21 is selected from the group consisting of leucine, methionine, proline, isoleucine and valine;
- AA22 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA23 is selected from the group consisting of tyrosine, leucine, phenylalanine, tryptophan, isoleucine, methionine and valine;
- AA24 is selected from the group consisting of cysteine, serine and threonine;
- AA25 is selected from the group consisting of tyrosine, phenylalanine, proline and tryptophan;
- AA26 is selected from the group consisting of asparagine, aspartic acid, glutamine, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA27 is selected from the group consisting of proline, isoleucine, threonine, glycine, leucine, methionine, valine, serine and alanine;
- AA28 is selected from the group consisting of serine, asparagine, cysteine, proline, threonine and glutamine;
- AA29 is selected from the group consisting of histidine, arginine and lysine;
- AA30 is selected from the group consisting of asparagine, valine, proline, serine, glutamine, isoleucine, leucine, methionine and threonine;
- AA31 is selected from the group consisting of proline, serine and threonine;
- AA32 is selected from the group consisting of glutamic acid, glycine, aspartic acid, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA33 is selected from the group consisting of glutamine, proline and asparagine;
- and
- AA34 is selected from the group Consisting of leucine, methionine, isoleucine and valine.
A peptide consisting of a sequence of amino acids AA1 through AA20 or a subsequence thereof comprising at least five amino acids, wherein:
- AA1 is selected from the group consisting of methionine, isoleucine, leucine and valine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of phenylalanine, tyrosine, and tryptophan;
- AA4 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA5 is proline;
- AA6 is selected from the group consisting of serine, tyrosine, threonine, phenylalanine, tryptophan, leucine and isoleucine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of serine, cysteine and threonine;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of lysine and arginine;
- AA11 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA12 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of proline, glutamine, and asparagine;
- AA15 is selected from the group consisting of lysine and arginine;
- AA16 is selected from the group consisting of asparagine, histidine and glutamine;
- AA17 is selected from the group consisting of lysine, arginine, serine and threonine;
- AA18 is selected from the group consisting of asparagine, glutamic acid, alanine, glutamine, aspartic acid, glycine, isoleucine, leucine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA19 is selected from the group consisting of lysine and arginine;
- and
- AA20 is selected from the group consisting of isoleucine, leucine, methionine and valine.
A peptide consisting of a sequence of amino acids AA1 through AA31 or a subsequence thereof comprising at least five amino acids, wherein:
- AA1 is selected from the group consisting of methionine, isoleucine, leucine and valine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA4 is selected from the group consisting of methionine, isoleucine, leucine and valine;
- AA5 is selected from the group consisting of alanine and glycine;
- AA6 is histidine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of lysine and arginine;
- AA11 is selected from the group consisting of serine and threonine;
- AA12 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of arginine and lysine;
- AA15 is selected from the group consisting of serine and threonine;
- AA16 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA17 is selected from the group consisting of arginine and lysine;
- AA18 is proline;
- AA19 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA20 is selected from the group consisting of alanine and glycine;
- AA21 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA22 is selected from the group consisting of asparagine and glutamine;
- AA23 is selected from the group consisting of asparagine and glutamine;
- AA24 is proline;
- AA25 is selected from the group consisting of glycine and alanine;
- AA26 is selected from the group consisting of arginine and lysine;
- AA27 is proline;
- AA28 is proline;
- AA29 is proline;
- AA30 is selected from the group consisting of threonine and serine;
- and
- AA31 is selected from the group consisting of leucine, isoleucine, methionine and valine, with the proviso that the peptide is not represented by the sequence MAHGDLKSYLRSLRPEAENNP (SEQ ID NO:171).
A peptide consisting of a sequence of amino acids AA1 through AA18 or a subsequence thereof comprising at least seven amino acids, wherein:
- AA1 is selected from the group consisting of threonine and serine;
- AA2 is selected from the group consisting of alanine and glycine;
- AA3 is selected from the group consisting of phenylalanine, tryptophan and tyrosine;
- AA4 is histidine;
- AA5 is selected from the group consisting of alanine, glutamic acid, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA6 is selected from the group consisting of lysine and arginine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of asparagine, serine, glutamine and threonine;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of glutamine, serine and threonine;
- AA11 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA12 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of threonine, lysine, serine and arginine;
- AA15 is selected from the group consisting of arginine, alanine, glycine and lysine;
- AA16 is selected from the group consisting of histidine, asparagine and glutamine;
- AA17 is selected from the group consisting of valine, isoleucine, leucine and methionine;
- and
- AA18 is selected from the group consisting of isoleucine, valine, leucine and methionine.
A peptide consisting of a sequence of amino acids AA1 through AA18 or a subsequence thereof comprising at least seven amino acids, wherein:
- AA1 is selected from the group consisting of threonine and serine;
- AA2 is selected from the group consisting of histidine, aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA4 is histidine;
- AA5 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA6 is selected from the group consisting of histidine, methionine, asparagine, isoleucine, leucine, valine and glutamine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of serine and threonine;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA11 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA12 is selected from the group consisting of phenylalanine, tyrosine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of glutamine, lysine, asparagine and arginine;
- AA15 is selected from the group consisting of arginine, leucine, cysteine, serine, lysine, isoleucine, methionine, valine and threonine;
- AA16 is selected from the group consisting of glutamine, threonine, alanine, tyrosine, asparagine, serine, phenylalanine, tryptophan and glycine;
- AA17 is selected from the group consisting of threonine and serine;
- and
- AA18 is selected from the group consisting of leucine, valine, isoleucine and methionine.
A peptide consisting of a sequence of amino acids AA1 through AA34 or a subsequence thereof comprising at least five amino acids, wherein:
- AA1 is selected from the group consisting of phenylalanine, tryptophan and tyrosine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA4 is selected from the group consisting of methionine, isoleucine, leucine and valine;
- AA5 is selected from the group consisting of arginine and lysine;
- AA6 is histidine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of asparagine and glutamine;
- AA11 is selected from the group consisting of arginine and lysine;
- AA12 is selected from the group consisting of phenylalanine, tryptophan and tyrosine;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of arginine and lysine;
- AA15 is selected from the group consisting of serine, alanine, threonine and glycine;
- AA16 is histidine;
- AA17 is selected from the group consisting of glycine and alanine;
- AA18 is proline;
- AA19 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA20 is selected from the group consisting of alanine and glycine;
- AA21 is selected from the group consisting of lysine, valine, methionine, arginine, isoleucine and leucine;
- AA22 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA23 is selected from the group consisting of leucine, methionine, isoleucine and valine;
- AA24 is selected from the group consisting of alanine, valine, isoleucine, leucine, methionine and glycine;
- AA25 is selected from the group consisting of glycine, glutamic acid, aspartic acid, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA26 is selected from the group consisting of glycine and alanine;
- AA27 is selected from the group consisting of glutamic acid, asparagine, glutamine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA28 is selected from the group consisting of aspartic acid, proline, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA29 is selected from the group consisting of valine, proline, arginine, isoleucine, leucine, methionine and lysine;
- AA30 is selected from the group consisting of alanine, threonine, glutamine, serine, asparagine and glycine;
- AA31 is selected from the group consisting of proline, glutamic acid, alanine, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA32 is selected from the group consisting of proline, glycine and alanine;
- AA33 is selected from the group consisting of leucine, glutamic acid, isoleucine, methionine, valine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- and
- AA34 is selected from the group consisting of leucine, isoleucine, methionine and valine, wherein the sequence AA1 through AA34 or a subsequence thereof corresponds to the sequence of the αD region of a neurotrophic receptor kinase selected from the group consisting of SEQ ID NO:68 and SEQ ID NO:69 or a subsequence thereof, with the proviso that any two amino acids in the sequence AA1 through AA34 or the subsequence thereof can vary as set forth above.
A peptide consisting of a sequence of amino acids AA1 through AA34 or a subsequence thereof comprising at least five amino acids, wherein:
- AA1 is selected from the group consisting of phenylalanine, tryptophan and tyrosine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA4 is selected from the group consisting of methionine, isoleucine, leucine and valine;
- AA5 is selected from the group consisting of arginine and lysine;
- AA6 is histidine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of asparagine and glutamine;
- AA11 is selected from the group consisting of arginine and lysine;
- AA12 is selected from the group consisting of phenylalanine, tryptophan and tyrosine;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of arginine and lysine;
- AA15 is selected from the group consisting of serine, alanine, threonine and glycine;
- AA16 is histidine;
- AA17 is selected from the group consisting of glycine and alanine;
- AA18 is proline;
- AA19 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA20 is selected from the group consisting of alanine and glycine;
- AA21 is selected from the group consisting of lysine, valine, methionine, arginine, isoleucine and leucine;
- AA22 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA23 is selected from the group consisting of leucine, methionine, isoleucine and valine;
- AA24 is selected from the group consisting of alanine, valine, isoleucine, leucine, methionine and glycine;
- AA25 is selected from the group consisting of glycine, glutamic acid, aspartic acid, alanine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA26 is selected from the group consisting of glycine and alanine;
- AA27 is selected from the group consisting of glutamic acid, asparagine, glutamine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA28 is selected from the group consisting of aspartic acid, proline, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA29 is selected from the group consisting of valine, proline, arginine, isoleucine, leucine, methionine and lysine;
- AA30 is selected from the group consisting of alanine, threonine, glutamine, serine, asparagine and glycine;
- AA31 is selected from the group consisting of proline, glutamic acid, alanine, aspartic acid, glycine and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA32 is selected from the group consisting of proline, glycine and alanine;
- AA33 is selected from the group consisting of leucine, glutamic acid, isoleucine, methionine, valine, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- and
- AA34 is selected from the group consisting of leucine, isoleucine, methionine and valine, wherein the sequence AA1 through AA18 or a subsequence thereof corresponds to the sequence of the αD region of a neurotrophic receptor kinase selected from the group consisting of SEQ ID NO:68 and SEQ ID NO:69 or a subsequence thereof, with the proviso that any one amino acid in the sequence AA1 through AA31 or the subsequence thereof can vary as set forth above.
A peptide consisting of a sequence of amino acids AA1 through AA21 or a subsequence thereof comprising at least five amino acids, wherein:
- AA1 is selected from the group consisting of threonine and serine;
- AA2 is histidine
- AA3 is selected from the group consisting of tryptophan, phenylalanine and tyrosine;
- AA4 is selected from the group consisting of isoleucine, leucine and methionine;
- AA5 is proline;
- AA6 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of serine and threonine;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA11 is selected from the group consisting of asparagine and glutamine;
- AA12 is selected from the group consisting of valine, isoleucine, leucine and methionine;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is histidine;
- AA15 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA16 is selected from the group consisting of glycine and alanine;
- AA17 is selected from the group consisting of threonine and serine;
- AA18 is selected from the group consisting of asparagine and glutamine;
- AA19 is selected from the group consisting of phenylalanine, tryptophan and tyrosine;
- AA20 is selected from the group consisting of valine, isoleucine, leucine and methionine;
- and
- AA21 is selected from the group consisting of valine, isoleucine, leucine and methionine.
A peptide consisting of a sequence of amino acids AA1 through AA22 or a subsequence thereof comprising at least five amino acids, wherein:
- AA1 is selected from the group consisting of methionine, isoleucine, leucine and valine;
- AA2 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA3 is selected from the group consisting of tyrosine, phenylalanine and tryptophan;
- AA4 is selected from the group consisting of cysteine and serine;
- AA5 is selected from the group consisting of serine, glutamine, threonine and asparagine;
- AA6 is selected from the group consisting of glycine and alanine;
- AA7 is selected from the group consisting of glycine and alanine;
- AA8 is selected from the group consisting of aspartic acid, glutamic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA9 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA10 is selected from the group consisting of arginine and lysine;
- AA11 is selected from the group consisting of lysine and asparagine;
- AA12 is selected from the group consisting of leucine, tyrosine, isoleucine, methionine, valine, phenylalanine and tryptophan;
- AA13 is selected from the group consisting of leucine, isoleucine, methionine and valine;
- AA14 is selected from the group consisting of asparagine and glutamine;
- AA15 is selected from the group consisting of lysine, glutamine, arginine and asparagine;
- AA16 is selected from the group consisting of proline, phenylalanine, tryptophan and tyrosine;
- AA17 is selected from the group consisting of glutamic acid, aspartic acid and an aliphatic, substituted aliphatic, benzyl, substituted benzyl, aromatic or substituted aromatic ester of glutamic acid or aspartic acid;
- AA18 is selected from the group consisting of asparagine and glutamine;
- AA19 is selected from the group consisting of cysteine and serine;
- AA20 is selected from the group consisting of cysteine and serine;
- AA21 is selected from the group consisting of glycine and alanine;
- and
- AA22 is selected from the group consisting of leucine, isoleucine, methionine and valine.
Dependencies are inferred from the claim text.