Peptide libraries
The invention relates to novel libraries of linear and cyclic peptides, and methods of generating and screening such libraries for biological, pharmaceutical and other uses.
1. A library of synthetic peptides, comprising
linear and cyclic peptides,
wherein the cyclic peptides have different loop lengths, and
wherein the cyclic peptides have 2, 3, 4, 5, 6 and 7 loops.
2. The library according to claim 1 , wherein the loop lengths range from 3-17 amino acids in length.
3. The library according to claim 2 , wherein the library comprises cyclic peptides comprising loop lengths of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 amino acids.
4. The library according to claim 3 , wherein the library comprises cyclic peptides comprising loop lengths of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17 amino acids.
5. The library according to claim 1 , wherein the synthetic peptides of said library are translated from nucleic acids.
6. The library according to claim 1 , wherein the synthetic peptides of said library are displayed on bacteriophage.
7. The library according to claim 1 , wherein the synthetic peptides of said library comprise a controlled ratio of cysteines at certain positions.
8. The library according to claim 1 , wherein the cyclic peptides are formed by one or more covalent or one or more non-covalent bonds.
9. The library according to claim 8 , wherein said covalent bond is a disulfide bond or a bond between two non-naturally occurring amino acids.
10. The library according to claim 9 , wherein said bond between two non-naturally occurring amino acids is a thioether bond.
11. The library according to claim 9 , wherein said covalent bond is a disulfide bond.
12. The library according to claim 11 , wherein said disulfide bond is formed by two cysteine residues.
13. The library according to claim 12 , wherein said library comprises peptides comprising 0, 1, 2, 3, 4, 5, 6 or 7 or more cysteine residues.
14. The library according to claim 13 , wherein said library comprises peptides comprising 0, 1, 2, 3, 4, 5, 6 and 7 cysteine residues.
15. The library according to claim 1 , wherein each synthetic peptide of the library comprises an amino acid sequence Cmix-(X)m-(Amix)n, wherein
Cmix is a mixture of 50% cysteine or an equal mixture of remaining natural occurring amino acids excluding cysteine,
X are each an equal mixture of natural occurring amino acids, excluding cysteine,
Amix are each a mixture of 5-50% cysteine or an equal mixture of remaining natural occurring amino acids excluding cysteine, and
m and n are both, and independently from each other, 3-20.
16. The library according to claim 15 , wherein each synthetic peptide of the library comprises an amino acid sequence Cmix-(X)m-(Amix)n, wherein
Amix are each a mixture of 10-20% cysteine and an equal mixture of remaining natural occurring amino acids excluding cysteine,
m is 5-6, and
n is 3-20.
17. The library according to claim 16 , wherein each synthetic peptide of the library comprises an amino acid sequence (X)I-Cmix-(X)m-(Amix)n, wherein
I is 1-3.
18. The library according to claim 17 , wherein each synthetic peptide of the library comprises an amino acid sequence (X)I-Cmix-(X)m-(Amix)n, wherein
Amix are each a mixture of 15% cysteine and an equal mixture of remaining natural occurring amino acids excluding cysteine,
I is 3,
m is 6, and
n is 10.
19. The library according to claim 18 , wherein the library has a design as shown in FIG. 1 .
20. A library of nucleic acids encoding the library of peptides according to claim 1 .
21. A vector comprising the nucleic acids of claim 20 .
22. The vector according to claim 21 , wherein said vector is a display vector or an expression vector.
23. A method of identifying a peptide specific for an antigen, comprising
(a) contacting an antigen with a library of claim 1 , and
(b) selecting one or more peptides specific for said antigen.