Bis (amino acid) molecular scaffolds

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 5 or 6;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at positions 2 and 4 and of the carbon bearing R1 (if R1 is not H) can be any one of (S,S,S), (S,S,R), (S,R,S), (S,R,R), (R,S,S), (R,S,R), (R,R,S) or (R,R,R).

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 4 or 6;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at positions 2 and 5 and of the carbon bearing R1 (if R1 is not H) can be any one of (S,S,S), (S,S,R), (S,R,S), (S,R,R), (R,S,S), (R,S,R), (R,R,S) or (R,R,R).

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 4, 5, 6, 8 or 9;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at positions 2, 4, 7, 9 and of the carbon bearing R1 (if R1 is not H) can be any of the 32 combinations of (R) and (S).

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 5, 6, 7 or 8;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at the positions 2, 3, 4 and 5, and of the carbon bearing R1 (if R1 is not H) can be any of the 32 combinations of (R) and (S).

A method of synthesizing bis peptides comprising the steps of:

• 1) providing a solid support;
• 2) activating a first bis amino acid or naturally occurring amino acid;
• 3) attaching the bis amino acid or naturally occurring amino acid to the support;
• 4) removing the leading edge amine protecting group if a bis amino acid is used, or the amine protecting group if a naturally occurring amino acid is used;
• 5) activating and attaching a next bis amino acid or a next naturally occurring amino acid to the leading edge amine of the bis amino acid or amine of the naturally occurring amino acid;
• and
• 6) repeating steps 4 and 5 as necessary to achieve the desired chain length;
• 7) detaching the synthesized bis peptide from the support;
• and
• 8) isolating the synthesized bis peptide,
• where the bis peptide synthesized in the above manner has at least two contiguous bis amino acids, and a rigidification step is carried out either after step 4 or after detachment of the bis peptide from the solid support.

A method of synthesizing bis peptides comprising the steps of:

• 1) providing a bis-amino acid or bis-peptide fragment containing a mixture of bis-amino acid and naturally occurring amino acid with an unprotected leading edge amine and a protected trailing edge carboxylic acid;
• 2) providing a bis-s or bis-peptide fragment containing a mixture of bis-amino acid and naturally occurring amino acids with a protected leading edge amine and an activated ester;
• 3) coupling the two fragments in solution;
• 4) isolating the synthesized bis-peptide;
• 5) removing the leading edge amine protecting group or the trailing end carboxylic acid protecting group;
• and
• 6) repeating steps 1, 2, 3, 4 to achieve the desired chain length;
• where the bis peptide synthesized in the above manner has at least two contiguous bis amino acids, and a rigidification step is carried out either after step 3 or after detachment of the bis peptide from the solid support.

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 5, 6, 7, 8 or 9;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at the positions 2, 3, 4 and 5, and of the carbon bearing R1 (if R1 is not H) can be any of the 32 combinations of (R) and (S).

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 4, 6, 7, 8 or 9;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at the positions 2, 4, 5 and 6, and of the carbon bearing R1 (if R1 is not H) can be any of the 32 combinations of (R) and (S).

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 4, 5, 7 or 8;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at the positions 2, 4, 6 and 8, and of the carbon bearing R1 (if R1 is not H) can be any of the 32 combinations of (R) and (S).

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 4, 5 or 6;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at the positions 2, 3, 5 and 7, and of the carbon bearing R1 (if R1 is not H) can be any of the 32 combinations of (R) and (S).

A compound having the formula

• where:
• X represents a first amine protecting group;
• Y represents a second amine protecting group;
• Z represents a weak leaving group;
• R1 represents an H, or a functional group, and can be attached to the molecule at positions 2, 3, 4, 5 or 7;
• R2 represents an H or a functional group;
• R5 represents N3 or NR2Y;
• R6 represents a carboxylic acid or a strongly activated ester;
• and
• the stereochemical configuration at the positions 2, 3, 5 and 6, and of the carbon bearing R1 (if R1 is not H) can be any of the 32 combinations of (R) and (S).