Method for synthesizing peptides comprising at least one glycine molecule

1. A method for preparing a peptide of general formula

R 1 R 2 NCH 2 —C(═O)—HN-A-COOH  (I)

in which A is a peptide chain comprising at least two enantiopure amino acids; and R 1 and R 2 are each H, HN represents the terminal amino group of A and COOH represents the terminal carboxyl group of A,

comprising

a) producing a compound of general formula

XCH 2 —C(═O)—HN-A-COOY  (II);

wherein

X is a group which can be substituted by nucleophilic substitution, chosen from Cl and Br;

Y is selected from the group consisting of H, Li + , Na + , K + , Cs + , Mg 2+ , Ca 2+ , Sr 2+ , and Ba 2+ ;

A has the same meaning as in formula (I);

HN represents the terminal amino group of A; and

COOY represents the terminal carboxyl group of A,

by peptide coupling of a fragment of general formula

XCH 2 —C(═O)—HN—B  (VI)

wherein

X is a group which can be substituted by nucleophilic substitution, chosen from Cl and Br,

B is an amino acid or a peptide chain optionally bearing protective and/or activating groups,

HN represents the α- amino group when B is an amino acid or the terminal amino group of B when B is a peptide,

with a fragment F, wherein fragment F is a persilylated amino acid or a persilylated peptide chain;

and

b) reacting said compound of general formula (II) as defined in a) with a compound of general formula HNR 1 R 2 (III) in which R 1 and R 2 are each H, wherein the reaction is carried out at a temperature of −30° C. to +60° C.

2. The method according to claim 1 , in which the reaction is carried out at a temperature of 0° C. to +50° C.

3. The method according to claim 1 , in which the reaction is carried out at a temperature of +10° C. to +40° C.

4. The method according to claim 1 , in which the reaction is carried out in a liquid medium containing at least 25% by weight, relative to the total weight of the liquid medium, of compound of general formula (III).

5. The method according to claim 4 , in which the liquid medium contains at least 30% by weight of compound of general formula (III).

6. The method according to claim 1 , in which the reaction is carried out in a liquid medium in which a concentration of the compound of general formula (II) of less than or equal to 10% by weight relative to the total weight of the liquid medium, is maintained.

7. The method according to claim 1 , in which the compound of general formula (III) is aqueous ammonia.

8. The method according to claim 1 , in which A is a peptide chain made up of 2 to 20 amino acids.

9. The method according to claim 1 , in which B is an amino acid.

10. The method according to claim 1 , in which the group A of the compound of general formula (II) is Phe-Leu-Gly.

11. The method according to claim 4 , in which the group A of the compound of general formula (II) is Phe-Leu-Gly.

12. The method according to claim 5 , in which the group A of the compound of general formula (II) is Phe-Leu-Gly.

13. The method according to claim 6 , in which the group A of the compound of general formula (II) is Phe-Leu-Gly.

14. The method according to claim 7 , in which the group A of the compound of general formula (II) is Phe-Leu-Gly.

15. The method according to claim 8 , in which the group A of the compound of general formula (II) is Phe-Leu-Gly.

16. The method according to claim 9 , in which the group A of the compound of general formula (II) is Phe-Leu-Gly.