Peptide compositions mimicking TGF-β activity
AssigneeThe Regents of the University of California
InventorsRajendra S. Bhatnagar, Jing Jing Qian, Craig Gough
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Abstract
Compositions suitable for pharmaceutical administration are provided in which one compound is a small peptide mimic of TGF-β. More preferably, pharmaceutical compositions of the present invention are formulated as combinations of two components, wherein one component includes a peptide mimic for TGF-β and the other component is structurally or biologically analogous to a small region of collagen and mimics the conformation recognized by collagen binding species. A particularly preferred combination is A-N-V-A-E-N-A (SEQ ID NO:1) and G-T-P-G-P-Q-G-I-A-G-Q-R-G-V-V (SEQ ID NO:17).
Claims19
A pharmaceutical composition, comprising:
- at least two components, one component being a TGF-β mimic having cellular proliferation inhibition activity, and being a six or seven amino acid peptide, having the sequence AAi-AAi+1-AAi+2 as an initial sequence defining the N-terminus of said peptide or having the sequence Ala-AAi-AAi+1-AAi+2, said peptide further having an AAi+n adjacent or proximal to said sequence in the C-terminus direction, wherein n is 3, 4, or 5 such that said peptide contains n−3 additional amino acid residues in between AAi+2 and AAi+n, and wherein
- AAi is alanine, asparagine, or leucine,
- AAi+1 is valine, isoleucine, α-amino isobutyric acid, or α-amino butyric acid,
- AAi+2 is alanine or N-methyl alanine, and
- AAi+n is glutamic acid, aspartic acid, glutamine, or asparagine, or other amino acid possessing a side-chain with a hydrogen bond acceptor, the other component being a collagen receptor ligand, said collagen receptor ligand having a domain including at least -Ile-Ala- folded in a β-bend at physiologic conditions;
- and
- a physiologically acceptable carrier.
A pharmaceutical composition comprising:
- A-N-V-A-E-N-A (SEQ ID NO:1) and G-T-P-G-P-O-G-I-A-G-O-R-G-V-V (SEQ ID NO:
- 17) in a physiologically acceptable carrier.
A pharmaceutical composition, comprising:
- at least two components, one component being a TGF-β mimic having cellular proliferation inhibition activity, and being a six or seven amino acid peptide, having the sequence AAi-AAi+1-AAi+2 as an initial sequence defining the N-terminus of said peptide or having the sequence Ala-AAi-AAi+1-AAi+2, said peptide further having an AAi+n adjacent or proximal to said sequence in the C-terminus direction, wherein n is 3, 4, or 5 such that said peptide contains n−3 additional amino acid residues in between AAi+2 and AAi+n, and wherein
- AAi is alanine, asparagine, or leucine,
- AAi+1 is valine, isoleucine, α-amino isobutyric acid, or α-amino butyric acid,
- AAi+2 is alanine or N-methyl alanine, and
- AAi+n is glutamic acid, aspartic acid, glutamine, or asparagine, or other amino acid possessing a side-chain with a hydrogen bond acceptor, the other component being a collagen receptor ligand, said collagen receptor ligand having a sequence selected from the group consisting of;
- G-T-P-G-P-Q-G-I-A-G-Q-R-G-V-V (SEQ ID NO:17), G-P-Q-G-I-A-G-Q-R (SEQ ID NO:26), Q-G-I-A-G-Q (SEQ ID NO:27), Q-G-I-A-G-Q-R(SEQ ID NO:
- 28), F-G-I-A-G-F (SEQ ID NO:29), G-I-A-G-Q (SEQ ID NO:30), Q-G-A-I-A-Q (SEQ ID NO:
- 31), C-G-I-A-G-C (SEQ ID NO:
- 33), E-G-I-A-G-K (SEQ ID NO:34), (NAc)-I-A-A (SEQ ID NO:35), I-A-(βA) (SEQ ID NO:36), and (NAc)-I-A-(N-MeA) (SEQ ID NO:37);
- and
- a physiologically acceptable carrier.
Dependencies are inferred from the claim text.