Structurally determined metallo-constructs and applications

A manufactured peptide and pharmaceutically acceptable salts thereof with a conformationally constrained secondary structure upon complexing with a metal ion, the conformationally constrained secondary structure comprising a member of a ligand and receptor pair, said peptide being of the general formula:

• R.sub.1 --X--R.sub.2
• wherein X is a complexing backbone for complexing a metal ion comprising two or more contiguous amino acids, so that substantially all of the valences of the metal ion are satisfied upon complexation of the metal ion with X;
• wherein X has, upon complexing with the metal ion, a specific regional secondary structure forming at least a part of the global secondary structure;
• wherein R.sub.1 and R.sub.2 each comprise from 0 to about 20 amino acids, said amino acids being selected so that upon complexing the metal ion with X at least a portion of either R.sub.1 or R.sub.2 or both have a structure forming the balance of the conformationally constrained secondary structure;
• and
• wherein the conformationally constrained secondary structure comprising at least a part of X and at least a part of R.sub.1 or R.sub.2 comprises a ligand forming a member of a ligand and receptor pair.

A method of making a peptide or pharmaceutically acceptable salts thereof that comprises a conformationally constrained secondary structure comprising a ligand forming a member of a ligand and receptor pair, the method comprising the steps of:

• a) providing a peptide of the general formula:
• R.sub.1 -X-R.sub.2
• wherein X is a complexing backbone for complexing metal ion comprising two or more contiguous amino acids, so that substantially all of said valences of the metal ion are satisfied upon complexation of the metal ion with X,
• wherein X has, upon complexing with the metal ion, a specific regional secondary structure forming a part of the conformationally constrained secondary structure,
• wherein R.sub.1 and R.sub.2 each comprise from 0 to about 20 amino acids, said amino acids being selected so that upon complexing the metal ion with X at least a portion of either R.sub.1 or R.sub.2 or both have a structure forming the balance of the conformationally constrained global secondary structure, and
• wherein the conformationally constrained global secondary structure comprising at least a part of X and at least a part of R.sub.1 or R.sub.2 comprises a ligand forming a member of a ligand and receptor pair;
• and
• b) complexing a metal ion to the peptide;
• whereby the metal ion causes X to form a specific regional secondary structure, thereby causing the peptide to be configured as a conformationally constrained secondary structure comprising a ligand capable of forming a member of a ligand and receptor pair.

A method of making a peptide or a pharmaceutically acceptable salt thereof that includes an amino acid sequence comprising a biological-function domain, the method comprising the steps of:

• a) providing a complexing backbone for complexing a metal ion comprising two or more contiguous amino acids, said amino acids being selected so that substantially all of the valences of the metal ion are satisfied upon complexation of the metal ion with the complexing backbone, at least a portion of which complexing backbone is coextensive with at least a portion of the biological-function domain upon complexing of the complexing backbone with a metal ion;
• b) providing from 0 to about 20 amino acids linked to either end of the complexing backbone, which amino acids comprise the remainder of the biological-function domain upon complexing of the complexing backbone with a metal ion;
• and
• c) complexing the complexing backbone with a metal ion.