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 alpha-helical regions wherein the one or more stable, internally-constrained regions comprises one of the following motifs:
wherein
is a single bond which is cis or trans; m is 1 or 2;
R is hydrogen, an amino acid side chain, an alkyl group, or an aryl group;
R 1 is an amino acid side chain, an alkyl group, or an aryl group;
R 3 is an amino acid, peptide, OR, CH 2 NH 2 , an alkyl group, or an aryl group; and
R 6 is a chain of one or more amino acids.
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. A peptide having one or more stable, internally-constrained alpha-helical, regions wherein the one or more stable, internally-constrained regions comprises one of the following motifs:
wherein is a single bond which is cis or trans; m is 1 or 2;
R is hydrogen, an amino acid side chain, an alkyl group, or an aryl group;
R 1 is an amino acid side chain, an alkyl group, or an aryl group;
R 3 is hydrogen; and
R 6 is a chain of one or more amino acids.
6. A peptide having one or more stable, internally-constrained alpha-helical, regions wherein the one or more stable, internally-constrained regions comprises the following motif:
wherein X is CH or CH 2 , and Y is CH 2 ; and each R is independently an amino acid side chain.