Methods for preparing internally constrained peptides and peptidomimetics
The present invention relates to a method for preparing a peptide having a stable, internally constrained alpha-helical, beta-sheet/beta-turn, 3 10 -helical, or pi-helical region and a method of stabilizing an alpha-helical, beta-sheet/beta-turn, 3 10 -helical, or pi-helical region within a peptide structure. The resulting peptides and methods of using them are also disclosed.
1. A peptide having one or more stable, internally-constrained beta-sheet/beta-turn, or 3 10 -helical regions wherein the one or more stable, internally-constrained regions comprises one of the following motifs:
wherein is a single or double bond, is a single bond which is cis or trans; m, n are independently 1 or 2; and
each R 1 , R 2 , R 3 , and R 4 is independently hydrogen, an amino acid side chain, an alkyl group, or an aryl group.
2. The peptide according to claim 1 , wherein the one or more stable, internally-constrained regions comprises the following motif:
3. The peptide according to claim 1 , wherein the one or more stable, internally-constrained regions comprises the following motif:
4. The peptide according to claim 1 , wherein the one or more stable, internally-constrained regions comprises the following motif:
5. The peptide according to claim 1 , wherein said one or more regions comprises a beta sheet or beta turn.
6. The peptide according to claim 1 , wherein said one or more regions comprises a 3 10 helix.
7. The peptide according to claim 1 , wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are amino acid side chains.
8. The peptide according to claim 1 , wherein m is 1.
9. The peptide according to claim 1 , wherein m is 2.
10. The peptide according to claim 1 , wherein n is 1.
11. The peptide according to claim 1 , wherein n is 2.